Effectiveness of bubble continuous positive airway pressure for treatment of children aged 1-59 months with severe pneumonia and hypoxaemia in Ethiopia: a pragmatic cluster-randomised controlled trial.

BACKGROUND: The safety and efficacy of bubble continuous positive airway pressure (bCPAP) for treatment of childhood severe pneumonia outside tertiary care hospitals is uncertain. We did a cluster-randomised effectiveness trial of locally made bCPAP compared with WHO-recommended low-flow oxygen therapy in children with severe pneumonia and hypoxaemia in general hospitals in Ethiopia. METHODS: This open, cluster-randomised trial was done in 12 general (secondary) hospitals in Ethiopia. We randomly assigned six hospitals to bCPAP as first-line respiratory support for children aged 1-59 months who presented with severe pneumonia and hypoxaemia and six hospitals to standard low-flow oxygen therapy. Cluster (hospital) randomisation was stratified by availability of mechanical ventilation. All children received treatment in paediatric wards (in a dedicated corner in front of a nursing station) with a similar level of facilities (equipment for oxygen therapy and medications) and staffing (overall, one nurse per six patients and one general practitioner per 18 patients) in all hospitals. All children received additional care according to WHO guidelines, supervised by paediatricians and general practitioners. The primary outcome was treatment failure (defined as any of the following: peripheral oxygen saturation <85% at any time after at least 1 h of intervention plus signs of respiratory distress; indication for mechanical ventilation; death during hospital stay or within 72 h of leaving hospital against medical advice; or leaving hospital against medical advice during intervention). The analysis included all children enrolled in the trial. We performed both unadjusted and adjusted analyses of the primary outcome, with the latter adjusted for the stratification variable and for the design effect of cluster randomisation, as well as selected potentially confounding variables, including age. We calculated effectiveness as the relative risk (RR) of the outcomes in the bCPAP group versus low-flow oxygen group. This trial is registered with ClinicalTrial.gov, NCT03870243, and is completed. FINDINGS: From June 8, 2021, to July 27, 2022, 1240 children were enrolled (620 in hospitals allocated to bCPAP and 620 in hospitals allocated to low-flow oxygen). Cluster sizes ranged from 103 to 104 children. Five (0·8%) of 620 children in the bCPAP group had treatment failure compared with 21 (3·4%) of 620 children in the low-flow oxygen group (unadjusted RR 0·24, 95% CI 0·09-0·63, p=0·0015; adjusted RR 0·24, 0·07-0·87, p=0·030). Six children died during hospital stay, all of whom were in the low-flow oxygen group (p=0·031). No serious adverse events were attributable to bCPAP. INTERPRETATION: In Ethiopian general hospitals, introduction of locally made bCPAP, supervised by general practitioners and paediatricians, was associated with reduced risk of treatment failure and in-hospital mortality in children with severe pneumonia and hypoxaemia compared with use of standard low-flow oxygen therapy. Implementation research is required in higher mortality settings to consolidate our findings. FUNDING: SIDA Sweden and Grand Challenges Ethiopia.

Performance of chest X-ray scoring in predicting disease severity and outcomes of patients hospitalised with COVID-19 in Bangladesh.

Introduction: Evaluation of potential outcomes of COVID-19-affected pneumonia patients using computed tomography scans may not be conceivable in low-resource settings. Thus, we aimed to evaluate the performance of chest X-ray scoring in predicting the disease severity and outcomes of adults hospitalised with COVID-19. Methods: This was a retrospective chart analysis consuming data from COVID-19-positive adults who had chest X-ray availability and were admitted to a temporary COVID unit, in Bangladesh from 23rd April 2020 to 15th November 2021. At least one clinical intensivist and one radiologist combinedly reviewed each admission chest X-ray for the different lung findings. Chest X-ray scoring varied from 0 to 8, depending on the area of lung involvement with 0 indicating no involvement and 8 indicating ⩾75% involvement of both lungs. The receiver operating characteristic curve was used to determine the optimum chest X-ray cut-off score for predicting the fatal outcomes. Result: A total of 218 (82.9%) out of 263 COVID-19-affected adults were included in the study. The receiver operating characteristic curve demonstrated the optimum cut-off as ⩾3 and ⩾5 for disease severity and death, respectively. In multivariate logistic regression analysis, a chest X-ray score of ⩾3 was found to be independently associated with disease severity (aOR: 8.70; 95% CI: 3.82, 19.58, p < 0.001) and a score of ⩾5 with death (aOR: 16.53; 95% CI: 4.74, 57.60, p < 0.001) after adjusting age, sex, antibiotic usage before admission, history of fever, cough, diabetes mellitus, hypertension, total leukocytes count and C-reactive protein. Conclusion: Using chest X-ray scoring derived cut-off at admission might help to identify the COVID-19-affected adults who are at risk of severe disease and mortality. This may help to initiate early and aggressive management of such patients, thereby reducing their fatal outcomes.

Prevalence and predictors of magnesium imbalance among critically ill diarrheal children and their outcome in a developing country.

Despite having essential roles in maintaining human body physiology, magnesium has gained little attention. We sought to evaluate the prevalence and predictors of magnesium imbalance in diarrheal children admitted to an intensive care unit. This retrospective data analysis was conducted among children admitted between January 2019 and December 2019. Eligible children were categorized by serum magnesium levels that were extracted from the hospital database. Among 557 participants, 29 (5.2%) had hypomagnesemia, 344 (61.8%) had normomagnesemia and 184 (33.0%) had hypermagnesemia. By multivariable multinomial logistic regression, we have identified older children (adjusted multinomial odds ratio, mOR 1.01, 95% CI: 1.004-1.018, p = 0.002) as a predictor of hypomagnesemia. Conversely, younger children (adjusted mOR 0.99, 95% CI: 0.982-0.998, p = 0.02), shorter duration of fever (adjusted mOR 0.92, 95% CI: 0.857-0.996, p = 0.04), convulsion (adjusted mOR 1.55, 95% CI: 1.005-2.380, p = 0.047), dehydration (adjusted mOR 3.27, 95% CI: 2.100-5.087, p<0.001), pneumonia (adjusted mOR 2.65, 95% CI: 1.660-4.240, p<0.001) and acute kidney injury (adjusted mOR 2.70, 95% CI: 1.735-4.200, p<0.001) as the independent predictors of hypermagnesemia. The mortality was higher among children with hypermagnesemia (adjusted mOR 2.31, 95% CI: 1.26-4.25, p = 0.007). Prompt identification and management of the magnesium imbalance among critically ill diarrheal children might have survival benefits, especially in resource-limited settings.

Evaluation of feasibility phase of adaptive version of locally made bubble continuous positive airway pressure oxygen therapy for the treatment of COVID-19 positive and negative adults with severe pneumonia and hypoxaemia.

Background: Bubble continuous positive airway pressure (bCPAP) oxygen therapy has been shown to be safe and effective in treating children with severe pneumonia and hypoxaemia in Bangladesh. Due to lack of adequate non-invasive ventilatory support during coronavirus disease 2019 (COVID-19) crisis, we aimed to evaluate whether bCPAP was safe and feasible when adapted for use in adults with similar indications. Methods: Adults (18-64 years) with severe pneumonia and moderate hypoxaemia (80 to <90% oxygen saturation (SpO2) in room air) were provided bCPAP via nasal cannula at a flow rate of 10 litres per minute (l/min) oxygen at 10 centimetres (cm) H2O pressure, in two tertiary hospitals in Dhaka, Bangladesh. Qualitative interviews and focus group discussions, using a descriptive phenomenological approach, were performed with patients and staff (n = 39) prior to and after the introduction (n = 12 and n = 27 respectively) to understand the operational challenges to the introduction of bCPAP. Results: We enrolled 30 adults (median age 52, interquartile range (IQR) 40-60 years) with severe pneumonia and hypoxaemia and/or acute respiratory distress syndrome (ARDS) irrespective of coronavirus disease 2019 (COVID-19) test results to receive bCPAP. At baseline mean SpO2 on room air was 87% (±2) which increased to 98% (±2), after initiation of bCPAP. The mean duration of bCPAP oxygen therapy was 14.4 ± 24.8 hours. There were no adverse events of note, and no treatment failure or deaths. Operational challenges to the clinical introduction of bCPAP were lack of functioning pulse oximeters, difficult nasal interface fixation among those wearing nose pin, occasional auto bubbling or lack of bubbling in water-filled plastic bottle, lack of holder for water-filled plastic bottle, rapid turnover of trained clinicians at the hospitals, and limited routine care of patients by hospital clinicians particularly after official hours. Discussion: If the tertiary hospitals in Bangladesh are supplied with well-functioning good quality pulse oximeters and enhanced training of the doctors and nurses on proper use of adapted version of bCPAP, in treating adults with severe pneumonia and hypoxaemia with or without ARDS, the bCPAP was found to be safe, well tolerated and not associated with treatment failure across all study participants. These observations increase the confidence level of the investigators to consider a future efficacy trial of adaptive bCPAP oxygen therapy compared to WHO standard low flow oxygen therapy in such patients. Conclusion: s Although bCPAP oxygen therapy was found to be safe and feasible in this pilot study, several challenges were identified that need to be taken into account when planning a definitive clinical trial.

Burden, predictors, and outcome of unconsciousness among under-five children hospitalized for community-acquired pneumonia: A retrospective study from a developing country.

Despite the reduction of death from pneumonia over recent years, pneumonia has still been the leading infectious cause of death in under-five children for the last several decades. Unconsciousness is a critical condition in any child resulting from any illness. Once it occurs during a pneumonia episode, the outcome is perceived to be fatal. However, data on children under five with pneumonia having unconsciousness are scarce. We've retrospectively analyzed the data of under-five children admitted at the in-patient ward of Dhaka Hospital of icddr,b during 1 January 2014 and 31 December 2017 with World Health Organization classified pneumonia or severe pneumonia. Children presented with or without unconsciousness were considered as cases and controls respectively. Among a total of 3,876 children fulfilling the inclusion criteria, 325 and 3,551 were the cases and the controls respectively. A multivariable logistic regression analysis revealed older children (8 months vs. 7.9 months) (adjusted odds ratio, aOR 1.02, 95% CI: 1.004-1.04, p = 0.015), hypoxemia (aOR 3.22, 95% CI: 2.39-4.34, p<0.001), severe sepsis (aOR 4.46, 95% CI: 3.28-6.06, p<0.001), convulsion (aOR 8.90, 95% CI: 6.72-11.79, p<0.001), and dehydration (aOR 2.08, 95% CI: 1.56-2.76, p<0.001) were found to be independently associated with the cases. The cases more often had a fatal outcome than the controls (23% vs. 3%, OR 9.56, 95% CI: 6.95-13.19, p<0.001). If the simple predicting factors of unconsciousness in children under five hospitalized for pneumonia with different severity can be initially identified and adequately treated with prompt response, pneumonia-related deaths can be reduced more effectively, especially in resource-limited settings.

Is Fibersol-2 efficacious in reducing duration of watery diarrhea and stool output in children 1-3 years old? A randomized, parallel, double-blinded, placebo-controlled, two arm clinical trial.

BACKGROUND: Fibersol-2 has innumerable beneficial effects on human health. It is a fermentable, non-viscous, water-soluble, indigestible dextrin containing 90% dietary fiber produced from corn starch. We aimed to evaluate whether additional intake of Fibersol-2 along with oral rehydration solution treatment can reduce the duration of watery diarrhea and daily stool output in children 1-3 years as well as recovery of such children within 72 hours, compared to placebo. METHODS: This placebo-controlled double-blinded, randomized parallel two arm trial conducted in Kumudini Women's Medical College Hospital in rural Bangladesh between March and October, 2018 used 5 gm of either Fibersol-2 or placebo dissolved in 50-ml drinking water which was given orally to ninety-two children with watery diarrhea on enrollment twice daily for a period of 7 days. Randomization was done using a randomization table. We randomly allocated 45 (49%) and 47 (51%) children in Fibersol-2 and placebo groups, respectively. Outcome measures were duration of resolution of watery diarrhea, daily stool output and the proportion of children recovered within 72 hours. Primary and safety analyses were by intention to treat. This trial was registered at ClinicalTrials.gov, number NCT03565393. RESULTS: There was no significant difference observed in terms of duration of resolution of diarrhea (adjusted mean difference 8.20, 95% CI -2.74 to 19.15, p = 0.14, adjusted effect size 0.03); the daily stool output (adjusted mean difference 73.57, 95% CI -94.17 to 241.32, p = 0.38, adjusted effect size 0.33) and the proportion of children recovered within 72 hours (adjusted odds ratio 0.49, 95% CI = 0.12 to 1.96, p = 0.31, adjusted risk difference -0.06 (95% CI -0.19 to -0.06), after regression analysis between Fibersol-2 and placebo. CONCLUSION: No beneficial role of Fibersol-2 was observed in diarrheal children aged 1-3 years. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention are registered. https://clinicaltrials.gov/ct2/show/NCT03565393.

In-person training on COVID-19 case management and infection prevention and control: Evaluation of healthcare professionals in Bangladesh.

BACKGROUND: As COVID-19 was declared a global pandemic, the major focus of healthcare organizations shifted towards preparing healthcare systems to handle the inevitable COVID-19 burden at different phases and levels. A series of in-person training programs were operated in collaboration with government and partner organizations for the healthcare workers (HCW) of Bangladesh. This study aimed to assess the knowledge of HCWs regarding SARS-CoV-2 infection, their case management, infection prevention and control to fight against the ongoing pandemic. METHODS: As a part of the National Preparedness and Response Plan for COVID-19 in Bangladesh, the training program was conducted at four district-level hospitals and one specialized hospital in Bangladesh from July 1, 2020 to June 30, 2021. A total of 755 HCWs participated in the training sessions. Among them, 357 (47%) were enrolled for the evaluation upon completion of the data, collected from one district hospital (Feni) and one specialized hospital (National Institute of Mental Health). RESULTS: The mean percentage of pre-test and post-test scores of all the participants were found to be 57% (95% CI 8.34-8.91; p 0.01) and 65% (95% CI 9.56-10.15; p <0.001) respectively. The difference of score (mean) between the groups was significant (p<0.001). After categorizing participants' knowledge levels as poor, average and fair, doctors' group has shown to have significant enhancement from level of average to fair compared to that of the nurses. Factors associated with knowledge augmentation of doctors were working in primary health care centers (aOR: 4.22; 95% CI: 1.80, 9.88), job experience less than 5 years (aOR: 4.10; 95% CI: 1.01, 16.63) and experience in caring of family member with COVID-19 morbidity (aOR: 2.06; 95% CI: 1.03, 4.10), after adjusting for relevant covariates such as age, sex and prior COVID-19 illness. CONCLUSION: Considering the series of waves of COVID-19 pandemic with newer variants, the present paper underscores the importance of implementing the structured in-person training program on case management, infection prevention and control for the HCWs that may help for successful readiness prior to future pandemics that may further help to minimize the pandemic related fatal consequences.

Digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children 1-3 years old at a rural facility, Bangladesh: Results from a four arm exploratory study.

BACKGROUND: Fibersol-2 has some beneficial effects on human health. We aimed to evaluate the digestive tolerability and acceptability of Fibersol-2 in healthy and diarrheal children, as well as improvement in stool consistencies in young diarrheal children. METHODS: Sixty children of either sex, aged 1-3 years having four groups (healthy children/low dose, healthy children/high dose, children with diarrhea/low dose and children with diarrhea/high dose) were enrolled into this exploratory study between 1st August to 23rd October 2017. Two presumptive doses, low (2.5g) and high (5g), twice daily with 50 ml drinking water for seven days were the interventions. Outcomes were to observe the development of possible abdominal symptoms, such as pain, distension, rumbling, and bloating during the intervention and post-intervention periods in healthy and diarrheal children as well as improvement in stool consistencies in diarrheal children. RESULTS: Among the diarrheal children, the median (IQR) duration of resolution of diarrhea was 3.9 (2.9, 5.1) days vs. 3.5 (2.0, 8.0) days, p = 0.885; in low dose and high dose groups, respectively. Significant difference was observed in terms of abdominal pain (27% vs. 7%, p = 0.038) and distension (40% vs. 0%, p<0.001) in diarrheal children, compared to healthy children during the pre-intervention period. We also observed significant difference in respect of abdominal distension (23% vs. 0%, p = 0.011), rumbling (27% vs. 0%, p = 0.005) and bloating (43% vs. 3%, p = 0.001) in diarrheal children, compared to healthy children during the intervention period. However, no significant difference was observed in relation to abdominal pain (p = 0.347) and distension (p = 0.165) during the pre-intervention period, compared to the intervention period in diarrheal children. Moreover, no significant difference was observed during the post-intervention period for the diarrheal and healthy children. CONCLUSION: Fibersol-2 was found to be well tolerated in healthy and diarrheal children aged 1-3 years. TRIAL REGISTRATION: This study was registered as part of a randomized trial at ClinicalTrials.gov, number NCT03565393. The authors confirmed that all ongoing and related trials for this drug/intervention were registered.

Prevalence and outcome of anemia among children hospitalized for pneumonia and their risk of mortality in a developing country.

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23-2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.

Toxoplasma gondii Infection Is Associated with Low Birth Weight: Findings from an Observational Study among Rural Bangladeshi Women.

Gestational Toxoplasma gondii (T. gondii) infection may cause substantial adverse effects on developing fetuses, newborns and also mothers. This study aims to estimate the seroprevalence of T. gondii among rural Bangladeshi pregnant women and determine the risk of a low birth weight (LBW). We followed a longitudinal design where 208 pregnant women were followed until the birth of their infants. Levels of IgG and IgM of T. gondii were assessed using chemiluminescent immunoassay. Modified Poisson regression was used to estimate crude and adjusted associations and multiple regression analysis was performed to understand the confounding and modifying effects of the variables. Thirty-nine (19%) children were born with LBW, among whom 15 (39%) mothers were positive for T. gondii IgG during pregnancy. After adjusting for several confounders and modifiers, pregnant women with T. gondii IgG or IgM seropositivity were significantly associated with LBW of infants (aRR: 2.00, 95% CI: 1.17-3.42). The strength of this association increased after adjusting for maternal education (aRR: 4.88, 95% CI: 1.74-13.69). The final model had an AROC of 0.84 with a sensitivity of 36% and specificity of 97%. Although causality is yet to be established, the study observed an association between T. gondii infection during pregnancy among rural Bangladeshi women and LBW of newborns.

Physical Quality of Life of Sepsis Survivor Severely Malnourished Children after Hospital Discharge: Findings from a Retrospective Chart Analysis.

BACKGROUND: Quality of life (QoL) among pediatric sepsis survivors in resource-limited countries is poorly understood. We aimed to evaluate the QoL among sepsis survivors, by comparing them with non-sepsis survivors three months after hospital discharge. METHODOLOGY: In this retrospective chart analysis with a case-control design, we compared children having sepsis and non-sepsis at hospital admission and during their post-hospitalization life, where the study population was derived from a hospital cohort of 405 severely malnourished children having pneumonia. RESULTS: The median age (months, inter-quartile range) of the children having sepsis and non-sepsis was 10 (5, 17) and 9 (5, 18), respectively. Approximately half of the children among the sepsis survivors had new episodes of respiratory symptoms at home. Though death was significantly higher (15.8% vs. 2.7%, p ≤ 0.001) at admission among the sepsis group, deaths during post-hospitalization life (7.8% vs. 8.8%, p = 0.878) were comparable. A verbal autopsy revealed that before death, most of the children from the sepsis group had respiratory complaints, whereas gastrointestinal complaints were more common among the non-sepsis group. CONCLUSIONS: Pediatric sepsis is life-threatening both during hospitalization and post-discharge. The QoL after sepsis is compromised, including re-hospitalization and the development of new episodes of respiratory symptoms especially before death.

Characteristics of severely malnourished under-five children immunized with Bacillus Calmette-Guérin following Expanded Programme on Immunization schedule and their outcomes during hospitalization at an urban diarrheal treatment centre, Bangladesh.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has recently been found to have beneficial effects among children infected other than Mycobacterium tuberculosis. Due to the paucity of data on the outcomes of children who had successful BCG vaccination following Expanded Programme on Immunization (EPI) schedule, we aimed to investigate the characteristics of such children and their outcomes who were hospitalized for severe malnutrition. METHODS: A prospective observational study was conducted to determine the viral etiology of pneumonia in severely malnourished children those were admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between April 2015 and December 2017, constituted the study population. Using a case-control design for the analysis, children having BCG vaccination prior hospital admission were treated as cases (n = 611) and those without vaccination, constituted as controls (n = 83). Bi-variate analysis was conducted using socio-demographic, clinical, laboratory, and treatment characteristics on admission and outcomes during hospitalization. Finally, log-linear binomial regression analysis was done to identify independent impact of BCG vaccination. RESULTS: The cases more often presented with older age, have had lower proportion of maternal illiteracy, higher rate of breastfeeding, severe wasting and lower rate of hypoglycemia, compared to the controls. The cases were also found to have lower risk of severe sepsis and deaths, compared to the controls (for all, p<0.05). However, in log-linear binomial regression analysis, after adjusting for potential confounders, BCG vaccination following EPI schedule (RR:0.54; 95%CI = 0.33-0.89; p = 0.015) and breastfeeding (RR:0.53; 95%CI = 0.35-0.81; p = 0.003) were found to be protective for the development of severe sepsis. CONCLUSION: BCG vaccination and breastfeeding were found to be protective for the development of severe sepsis in hospitalized severely malnourished under-five children which underscores the importance of continuation of BCG vaccination at birth and breastfeeding up to two years of age.

Intravenous Amoxicillin Plus Intravenous Gentamicin for Children with Severe Pneumonia in Bangladesh: An Open-Label, Randomized, Non-Inferiority Controlled Trial.

The World Health Organization (WHO) recommends intravenous (IV) ampicillin and gentamicin as first-line therapy to treat severe pneumonia in children under five years of age. Ampicillin needs to be administered at a six-hourly interval, which requires frequent nursing intervention and bed occupancy for 5-7 days, limiting its utility in resource-poor settings. We compared the efficacy of IV amoxicillin over IV ampicillin, which is a potential alternative drug in treating severe pneumonia in children between 2-59 months. We conducted an unblinded, randomized, controlled, non-inferiority trial in the Dhaka hospital of icddr,b from 1 January 2018 to 31 October 2019. Children from 2-59 months of age presenting with WHO defined severe pneumonia with respiratory danger signs were randomly assigned 1:1 to either 50 mg/kg ampicillin or 40 mg/kg amoxicillin per day with 7.5 mg/kg gentamicin. The primary outcome was treatment failure as per the standard definition of persistence of danger sign(s) of severe pneumonia beyond 48 h or deterioration within 24 h of therapy initiation. The secondary outcomes were: (i) time required for resolution of danger signs since enrolment, (ii) length of hospital stay, (iii) death during hospitalization, and (iv) rate of nosocomial infections. Among 308 enrolled participants, baseline characteristics were similar among the two groups. Sixty-two (20%) children ended up with treatment failure, 21 (14%) in amoxicillin, and 41 (27%) in ampicillin arm, which is statistically significant (relative risk [RR] 0.51, 95% CI 0.32-0.82; p = 0.004). We reported 14 deaths for serious adverse events, 4 (3%) and 10 (6%) among amoxicillin and ampicillin arm, respectively. IV amoxicillin and IV gentamicin combination is not inferior to combined IV ampicillin and IV gentamicin in treating severe pneumonia in under-five children in Bangladesh. Considering the less frequent dosing and more compliance, IV amoxicillin is a better choice for treating children with severe pneumonia in resource-limited settings.

Anthropometric Indices of Giardia-Infected Under-Five Children Presenting with Moderate-to-Severe Diarrhea and Their Healthy Community Controls: Data from the Global Enteric Multicenter Study.

Among all intestinal parasitosis, giardiasis has been reported to be associated with delayed growth in malnourished children under 5 living in low- and middle-income countries. Relevant data on the nutritional status of children aged 0-59 months presenting with moderate-to-severe diarrhea (MSD) and giardia infection were collected from sentinel health facilities of the Global Enteric Multicenter Study's (GEMS) seven field settings, placed in diverse countries of Sub-Saharan Africa and South Asia between, December 2007 and February 2011. Then, this study analyzed a robust dataset of study participants (n = 22,569). Children having giardiasis with MSD constituted as cases (n = 1786), and those without MSD constituted as controls (n = 3470). Among the seven field sites, symptomatic giardiasis was 15% and 22% in Asian and African sites, respectively, whereas asymptomatic giardia infection (healthy without MSD) in Asian and African sites was 21.7% and 30.7%, respectively. Wasting and underweight were more frequently associated and stunting less often associated with symptomatic giardiasis (for all, p < 0.001). Symptomatic giardiasis had a significant association with worsening of nutritional status in under-five children. Improved socio-economic profile along with proper sanitation and hygienic practices are imperative to enhance child nutritional status, particularly in resource limited settings.

Risk Factors and Outcomes of Hospital Acquired Pneumonia in Young Bangladeshi Children.

Hospital acquired pneumonia (HAP) is common and often associated with high mortality in children aged five or less. We sought to evaluate the risk factors and outcome of HAP in such children. We compared demographic, clinical, and laboratory characteristics in children <5 years using a case control design during the period of August 2013 and December 2017, where children with HAP were constituted as cases (n = 281) and twice as many randomly selected children without HAP were constituted as controls (n = 562). HAP was defined as a child developing a new episode of pneumonia both clinically and radiologically after at least 48 h of hospitalization. A total of 4101 children were treated during the study period. The mortality was significantly higher among the cases than the controls (8% vs. 4%, p = 0.014). In multivariate logistic regression analysis, after adjusting for potential confounders, it was found that persistent diarrhea (95% CI = 1.32-5.79; p = 0.007), severe acute malnutrition (95% CI = 1.46-3.27; p < 0.001), bacteremia (95% CI = 1.16-3.49; p = 0.013), and prolonged hospitalization of >5 days (95% CI = 3.01-8.02; p < 0.001) were identified as independent risk factors for HAP. Early identification of these risk factors and their prompt management may help to reduce HAP-related fatal consequences, especially in resource limited settings.

Factors associated with severe sepsis in diarrheal adults and their outcome at an urban hospital, Bangladesh: A retrospective analysis.

BACKGROUND: To describe factors associated with severe sepsis in diarrheal adults and their outcomes and offender in blood and stool to understand their interplay as clinical features of sepsis and severe diarrhea often overlap. METHODS AND RESULTS: We used this retrospective chart analysis employing an unmatched case-control design to study critically ill diarrheal adults aged ≥18 years treated in ICU of Dhaka hospital, icddr,b between January 2011 to December 2015. Of 8,863 in-patient diarrheal adults, 350 having severe sepsis were cases and an equal number of randomly selected non-septic patients were the controls. Cases died significantly more (14.9% vs 4.6%, p = <0.001) than controls. 69% of the cases progressed to septic shock. In logistic regression analysis, steroid intake, ileus, acute kidney injury (AKI), metabolic acidosis, and hypocalcemia were significantly associated with severe sepsis in diarrheal adults (all, p<0.05). 12% of cases (40/335) had bacteremia. Streptococcus pneumoniae [9 (22.5%)] was the single most common pathogen and gram-negatives [27 (67.5%)] were prevailing as a group. CONCLUSION: Diarrheal adults who had ileus, AKI, metabolic acidosis, hypocalcemia, and also took steroids were found to have an association with severe sepsis. Strikingly, gram-negative were the predominant bacteria among the diarrheal adults having severe sepsis.

Vibrio cholerae O139 persists in Dhaka, Bangladesh since 1993.

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.

Seizure in Children Under Five Presenting With Pneumonia in a Critical Care Ward in Bangladesh: Prevalence, Associated Factors, and Outcome.

BACKGROUND: Pneumonia is the leading infectious cause of deaths in children under 5 for the last few decades. Development of seizure in those children is common and associated with increased risk of deaths. We therefore investigated the prevalence, associated factors and outcome of seizure in children hospitalized with pneumonia. METHODS: We conducted a retrospective chart analysis in the intensive care unit of the Dhaka Hospital of icddr,b. Children under 5 with World Health Organization (WHO) classified clinical (excluding seizure as 1 of the clinical diagnostics) and radiologic pneumonia, admitted to the intensive care unit at Dhaka Hospital of icddr,b between August 2013 and December 2017 were analyzed. We initially identified the children with pneumonia who had seizure. For comparison, we have taken 2 folds randomly selected controls from rest of the children with pneumonia having no seizure. Prevalence and outcome of children with pneumonia and seizure were measured. Factors associated with seizure in children with pneumonia compared with those without seizure were also identified. Seizure was characterized by sudden, violent, involuntary, and abnormal repetitive movements with or without loss or impairment of consciousness confirmed by attending physician. RESULTS: Among a total of 4101 children with pneumonia, 514 (12.5%) had seizure. Compared with children with pneumonia alone children having pneumonia and seizure more often developed respiratory failure (18% vs. 3%, P < 0.001) and died (13% vs. 3%, P < 0.001) during hospitalization. In logistic regression analysis hypoxemia (95% CI: 1.59-3.17, P < 0.001), severe pneumonia (95% CI: 2.13-6.52, P < 0.001), severe sepsis (95% CI: 1.30-2.88, P = 0.001), and hypernatremia (95% CI: 5.31-10.93, P < 0.001) were found to be independent risk factors for seizure. On the contrary, children with pneumonia having seizure were less likely to have severe acute malnutrition (95% CI: 0.26-0.50, P < 0.001). CONCLUSIONS: Early identification of risk factors for seizure in children with pneumonia may be helpful for clinicians to promptly treat them and therefore may have potential to reduce deaths in those children especially in resource limited settings.

Gender-related influences on adherence to advice and treatment-seeking guidance for infants and young children post-hospital discharge in Bangladesh.

BACKGROUND: Post-hospital discharge mortality risk is high among young children in many low and middle-income countries (LMICs). The available literature suggests that child, caregiver and health care provider gender all play important roles in post-discharge adherence to medical advice, treatment-seeking and recovery for ill children in LMICs, including those with undernutrition. METHODS: A qualitative study was embedded within a larger multi-country multi-disciplinary observational cohort study involving children aged less than 2 years conducted by the Childhood Acute Illness and Nutrition (CHAIN) Network. Primary data were collected from family members of 22 purposively selected cohort children. Family members were interviewed several times in their homes over the 6 months following hospital discharge (total n = 78 visits to homes). These in-depth interviews were complemented by semi-structured individual interviews with 6 community representatives, 11 community health workers and 12 facility-based health workers, and three group discussions with a total of 24 community representatives. Data were analysed using NVivo11 software, using both narrative and thematic approaches. RESULTS: We identified gender-related influences at health service/system and household/community levels. These influences interplayed to family members' adherence to medical advice and treatment-seeking after hospital discharge, with potentially important implications for children's recovery. Health service/system level influences included: fewer female medical practitioners in healthcare facilities, which influenced mothers' interest and ability to consult them promptly for their child's illnesses; gender-related challenges for community health workers in supporting mothers with counselling and advice; and male caregivers' being largely absent from the paediatric wards where information sessions to support post-discharge care are offered. Gendered household/community level influences included: women's role as primary caretakers for children and available levels of support; male family members having a dominant role in decision-making related to food and treatment-seeking behaviour; and greater reluctance among parents to invest money and time in the treatment of female children, as compared to male children. CONCLUSIONS: A complex web of gender related influences at health systems/services and household/community levels have important implications for young children's recovery post-discharge. Immediate interventions with potential for positive impact include awareness-raising among all stakeholders - including male family members - on how gender influences child health and recovery, and how to reduce adverse consequences of gender-based discrimination. Specific interventions could include communication interventions in facilities and homes, and changes in routine practices such as who is present in facility interactions. To maximise and sustain the impact of immediate actions and interventions, the structural drivers of women's position in society and gender inequity must also be tackled. This requires interventions to ensure equal equitable opportunities for men and women in all aspects of life, including access to education and income generation activities. Given patriarchal norms locally and globally, men will likely need special targeting and support in achieving these objectives.