Azithromycin for Bacterial Watery Diarrhea: A Reanalysis of the AntiBiotics for Children With Severe Diarrhea (ABCD) Trial Incorporating Molecular Diagnostics.

BACKGROUND: Bacterial pathogens cause substantial diarrhea morbidity and mortality among children living in endemic settings, yet antimicrobial treatment is only recommended for dysentery or suspected cholera. METHODS: AntiBiotics for Children with severe Diarrhea was a 7-country, placebo-controlled, double-blind efficacy trial of azithromycin in children 2-23 months of age with watery diarrhea accompanied by dehydration or malnutrition. We tested fecal samples for enteric pathogens utilizing quantitative polymerase chain reaction to identify likely and possible bacterial etiologies and employed pathogen-specific cutoffs based on genomic target quantity in previous case-control diarrhea etiology studies to identify likely and possible bacterial etiologies. RESULTS: Among 6692 children, the leading likely etiologies were rotavirus (21.1%), enterotoxigenic Escherichia coli encoding heat-stable toxin (13.3%), Shigella (12.6%), and Cryptosporidium (9.6%). More than one-quarter (1894 [28.3%]) had a likely and 1153 (17.3%) a possible bacterial etiology. Day 3 diarrhea was less common in those randomized to azithromycin versus placebo among children with a likely bacterial etiology (risk difference [RD]likely, -11.6 [95% confidence interval {CI}, -15.6 to -7.6]) and possible bacterial etiology (RDpossible, -8.7 [95% CI, -13.0 to -4.4]) but not in other children (RDunlikely, -0.3% [95% CI, -2.9% to 2.3%]). A similar association was observed for 90-day hospitalization or death (RDlikely, -3.1 [95% CI, -5.3 to -1.0]; RDpossible, -2.3 [95% CI, -4.5 to -.01]; RDunlikely, -0.6 [95% CI, -1.9 to .6]). The magnitude of risk differences was similar among specific likely bacterial etiologies, including Shigella. CONCLUSIONS: Acute watery diarrhea confirmed or presumed to be of bacterial etiology may benefit from azithromycin treatment. CLINICAL TRIALS REGISTRATION: NCT03130114.

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Importance: Sepsis is a leading cause of death among children worldwide. Current pediatric-specific criteria for sepsis were published in 2005 based on expert opinion. In 2016, the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) defined sepsis as life-threatening organ dysfunction caused by a dysregulated host response to infection, but it excluded children. Objective: To update and evaluate criteria for sepsis and septic shock in children. Evidence Review: The Society of Critical Care Medicine (SCCM) convened a task force of 35 pediatric experts in critical care, emergency medicine, infectious diseases, general pediatrics, nursing, public health, and neonatology from 6 continents. Using evidence from an international survey, systematic review and meta-analysis, and a new organ dysfunction score developed based on more than 3 million electronic health record encounters from 10 sites on 4 continents, a modified Delphi consensus process was employed to develop criteria. Findings: Based on survey data, most pediatric clinicians used sepsis to refer to infection with life-threatening organ dysfunction, which differed from prior pediatric sepsis criteria that used systemic inflammatory response syndrome (SIRS) criteria, which have poor predictive properties, and included the redundant term, severe sepsis. The SCCM task force recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Children with a Phoenix Sepsis Score of at least 2 points had in-hospital mortality of 7.1% in higher-resource settings and 28.5% in lower-resource settings, more than 8 times that of children with suspected infection not meeting these criteria. Mortality was higher in children who had organ dysfunction in at least 1 of 4-respiratory, cardiovascular, coagulation, and/or neurological-organ systems that was not the primary site of infection. Septic shock was defined as children with sepsis who had cardiovascular dysfunction, indicated by at least 1 cardiovascular point in the Phoenix Sepsis Score, which included severe hypotension for age, blood lactate exceeding 5 mmol/L, or need for vasoactive medication. Children with septic shock had an in-hospital mortality rate of 10.8% and 33.5% in higher- and lower-resource settings, respectively. Conclusions and Relevance: The Phoenix sepsis criteria for sepsis and septic shock in children were derived and validated by the international SCCM Pediatric Sepsis Definition Task Force using a large international database and survey, systematic review and meta-analysis, and modified Delphi consensus approach. A Phoenix Sepsis Score of at least 2 identified potentially life-threatening organ dysfunction in children younger than 18 years with infection, and its use has the potential to improve clinical care, epidemiological assessment, and research in pediatric sepsis and septic shock around the world.

Development and Validation of the Phoenix Criteria for Pediatric Sepsis and Septic Shock.

Importance: The Society of Critical Care Medicine Pediatric Sepsis Definition Task Force sought to develop and validate new clinical criteria for pediatric sepsis and septic shock using measures of organ dysfunction through a data-driven approach. Objective: To derive and validate novel criteria for pediatric sepsis and septic shock across differently resourced settings. Design, Setting, and Participants: Multicenter, international, retrospective cohort study in 10 health systems in the US, Colombia, Bangladesh, China, and Kenya, 3 of which were used as external validation sites. Data were collected from emergency and inpatient encounters for children (aged <18 years) from 2010 to 2019: 3 049 699 in the development (including derivation and internal validation) set and 581 317 in the external validation set. Exposure: Stacked regression models to predict mortality in children with suspected infection were derived and validated using the best-performing organ dysfunction subscores from 8 existing scores. The final model was then translated into an integer-based score used to establish binary criteria for sepsis and septic shock. Main Outcomes and Measures: The primary outcome for all analyses was in-hospital mortality. Model- and integer-based score performance measures included the area under the precision recall curve (AUPRC; primary) and area under the receiver operating characteristic curve (AUROC; secondary). For binary criteria, primary performance measures were positive predictive value and sensitivity. Results: Among the 172 984 children with suspected infection in the first 24 hours (development set; 1.2% mortality), a 4-organ-system model performed best. The integer version of that model, the Phoenix Sepsis Score, had AUPRCs of 0.23 to 0.38 (95% CI range, 0.20-0.39) and AUROCs of 0.71 to 0.92 (95% CI range, 0.70-0.92) to predict mortality in the validation sets. Using a Phoenix Sepsis Score of 2 points or higher in children with suspected infection as criteria for sepsis and sepsis plus 1 or more cardiovascular point as criteria for septic shock resulted in a higher positive predictive value and higher or similar sensitivity compared with the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) criteria across differently resourced settings. Conclusions and Relevance: The novel Phoenix sepsis criteria, which were derived and validated using data from higher- and lower-resource settings, had improved performance for the diagnosis of pediatric sepsis and septic shock compared with the existing IPSCC criteria.

Diagnostic, Management, and Research Considerations for Pediatric Acute Respiratory Distress Syndrome in Resource-Limited Settings: From the Second Pediatric Acute Lung Injury Consensus Conference.

OBJECTIVES: Diagnosis of pediatric acute respiratory distress syndrome (PARDS) in resource-limited settings (RLS) is challenging and remains poorly described. We conducted a review of the literature to optimize recognition of PARDS in RLS and to provide recommendations/statements for clinical practice and future research in these settings as part of the Second Pediatric Acute Lung Injury Consensus Conference (PALICC-2). DATA SOURCES: MEDLINE (Ovid), Embase (Elsevier), and CINAHL Complete (EBSCOhost). STUDY SELECTION: We included studies related to precipitating factors for PARDS, mechanical ventilation (MV), pulmonary and nonpulmonary ancillary treatments, and long-term outcomes in children who survive PARDS in RLS. DATA EXTRACTION: Title/abstract review, full-text review, and data extraction using a standardized data collection form. DATA SYNTHESIS: The Grading of Recommendations Assessment, Development, and Evaluation approach was used to identify and summarize evidence and develop recommendations. Seventy-seven studies were identified for full-text extraction. We were unable to identify any literature on which to base recommendations. We gained consensus on six clinical statements (good practice, definition, and policy) and five research statements. Clinicians should be aware of diseases and comorbidities, uncommon in most high-income settings, that predispose to the development of PARDS in RLS. Because of difficulties in recognizing PARDS and to avoid underdiagnosis, the PALICC-2 possible PARDS definition allows exclusion of imaging criteria when all other criteria are met, including noninvasive metrics of hypoxemia. The availability of MV support, regular MV training and education, as well as accessibility and costs of pulmonary and nonpulmonary ancillary therapies are other concerns related to management of PARDS in RLS. Data on long-term outcomes and feasibility of follow-up in PARDS survivors from RLS are also lacking. CONCLUSIONS: To date, PARDS remains poorly described in RLS. Clinicians working in these settings should be aware of common precipitating factors for PARDS in their patients. Future studies utilizing the PALICC-2 definitions are urgently needed to describe the epidemiology, management, and outcomes of PARDS in RLS.

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.

Chronic Kidney Disease Awareness Campaign and Mobile Health Education to Improve Knowledge, Quality of Life, and Motivation for a Healthy Lifestyle Among Patients With Chronic Kidney Disease in Bangladesh: Randomized Controlled Trial.

BACKGROUND: Chronic kidney disease (CKD) is linked to major health consequences and a poor quality of life. Despite the fact that CKD is becoming more prevalent, public knowledge of the disease remains low. OBJECTIVE: This study aimed to evaluate the outcome of a health education intervention designed to enhance knowledge, health-related quality of life (QOL), and motivation about healthy lifestyle among adults with CKD. METHODS: This study was a parallel-group (1:1), randomized controlled trial in the Mirzapur subdistrict of Bangladesh that compared 2 groups of patients with CKD. Adults with CKD (stages 1-3) were enrolled in November 2020 and randomly assigned the intervention or control group. The intervention group received health education through a CKD awareness campaign and mobile health technologies and was observed for 6 months, whereas the control group received standard treatment. The primary outcome was the evaluation of improved scores on the CKD knowledge questionnaire, and the secondary outcomes were improved QOL and changes in the levels of blood pressure (BP), BMI, serum creatinine, fasting blood sugar (FBS), hemoglobin, cholesterol, high-density lipoprotein cholesterol, triglyceride, serum uric acid, blood urea nitrogen (BUN), and albumin-to-creatinine ratio. RESULTS: The study enrolled 126 patients (control: n=63; intervention: n=63) and performed intention-to-treat analysis. The analyses included repeated measures ANOVA, and the results were observed to be significantly different from within groups (P<.001), between groups (P<.001), and the interaction of group × time factor (P<.001) for knowledge score. Diastolic BP and BMI showed significant differences arising from within groups (P<.001 and P=.01, respectively) and the interaction of group × time factor (P=.001 and P=.02, respectively); food salinity and hip circumferences showed significant differences arising from within groups (P=.001 and P=.03, respectively) and between groups (P=.001 and P=.02, respectively). Moreover, systolic BP and waist circumference showed significant differences from within groups (P<.001 and P=.003, respectively). However, no significant differences were found arising from within groups, between groups, and the interactions of group × time for QOL, urine salinity, and mid-upper arm circumference. Regarding the laboratory findings, from baseline to 6 months, the mean (SD) FBS decreased by 0.51 (3.77) mmol/L in the intervention group and 0.10 (1.44) mmol/L in the control group (P=.03); however, blood urea nitrogen increased by 3.64 (7.17) mg/dL in the intervention group and 1.68 (10.10) mg/dL in the control group (P=.01). CONCLUSIONS: The health education strategy, which included a campaign and mobile health, showed promise for enhancing CKD knowledge among patients with CKD. This strategy may also aid patients with CKD in controlling their FBS and BP. The combined health education initiatives give evidence for scaling them up in Bangladesh and possibly other low- and middle-income countries, particularly in rural and peri-urban settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04094831; https://clinicaltrials.gov/ct2/show/NCT04094831. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/30191.

Xpert Ultra Assay on Stool to Diagnose Pulmonary Tuberculosis in Children.

BACKGROUND: The World Health Organization recommends the Xpert MTB/RIF Ultra assay for diagnosing pulmonary tuberculosis (PTB) in children. Though stool is a potential alternative to respiratory specimens among children, the diagnostic performance of Xpert Ultra on stool is unknown. Thus, we assessed the diagnostic performance of Xpert Ultra on stool to diagnose PTB in children. METHODS: We conducted a cross-sectional study among consecutively recruited children (< 15 years of age) with presumptive PTB admitted in 4 tertiary care hospitals in Dhaka, Bangladesh, between January 2018 and April 2019. Single induced sputum and stool specimens were subjected to culture, Xpert, and Xpert Ultra. We considered children as bacteriologically confirmed on induced sputum if any test performed on induced sputum was positive for Mycobacterium tuberculosis and bacteriologically confirmed if M. tuberculosis was detected on either induced sputum or stool. RESULTS: Of 447 children, 29 (6.5%) were bacteriologically confirmed on induced sputum and 72 (16.1%) were bacteriologically confirmed. With "bacteriologically confirmed on induced sputum" as a reference, the sensitivity and specificity of Xpert Ultra on stool were 58.6% and 88.1%, respectively. Xpert on stool had sensitivity and specificity of 37.9% and 100.0%, respectively. Among bacteriologically confirmed children, Xpert Ultra on stool was positive in 60 (83.3%), of whom 48 (80.0%) had "trace call." CONCLUSIONS: In children, Xpert Ultra on stool has better sensitivity but lesser specificity than Xpert. A high proportion of Xpert Ultra assays positive on stool had trace call. Future longitudinal studies on clinical evolution are required to provide insight on the management of children with trace call.

The Etiology of Pneumonia From Analysis of Lung Aspirate and Pleural Fluid Samples: Findings From the Pneumonia Etiology Research for Child Health (PERCH) Study.

BACKGROUND: An improved understanding of childhood pneumonia etiology is required to inform prevention and treatment strategies. Lung aspiration is the gold standard specimen for pneumonia diagnostics. We report findings from analyses of lung and pleural aspirates collected in the Pneumonia Etiology Research for Child Health (PERCH) study. METHODS: The PERCH study enrolled children aged 1-59 months hospitalized with World Health Organization-defined severe or very severe pneumonia in 7 countries in Africa and Asia. Percutaneous transthoracic lung aspiration (LA) and pleural fluid (PF) aspiration was performed on a sample of pneumonia cases with radiological consolidation and/or PF in 4 countries. Venous blood and nasopharyngeal/oropharyngeal swabs were collected from all cases. Multiplex quantitative polymerase chain reaction (PCR) and routine microbiologic culture were applied to clinical specimens. RESULTS: Of 44 LAs performed within 3 days of admission on 622 eligible cases, 13 (30%) had a pathogen identified by either culture (5/44) or by PCR (11/29). A pathogen was identified in 12/14 (86%) PF specimens tested by either culture (9/14) or PCR (9/11). Bacterial pathogens were identified more frequently than viruses. All but 1 of the cases with a virus identified were coinfected with bacterial pathogens. Streptococcus pneumoniae (9/44 [20%]) and Staphylococcus aureus (7/14 [50%]) were the predominant pathogens identified in LA and PF, respectively. CONCLUSIONS: Bacterial pathogens predominated in this selected subgroup of PERCH participants drawn from those with radiological consolidation or PF, with S. pneumoniae and S. aureus the leading pathogens identified.

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.

Early management of hypokalaemia in severely malnourished children under five could help to reduce deaths in developing countries.

AIM: This study evaluated the factors associated with hypokalaemia and their outcomes, in severely malnourished children under 5 years of age. METHODS: We focused on 407 severely malnourished children under five who were admitted to the Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh, from April 2011 to June 2012. The cases were 139 with hypokalaemia, and the comparisons were 268 without hypokalaemia. RESULTS: Cases were older than the comparisons, with a poor socio-economic status and a higher death rate of 12% vs 7%. They were more likely to present with a history of measles, diarrhoea, lethargy, lower pulse rates, hyponatraemia, metabolic acidosis, hypocalcaemia, hypomagnesaemia, higher height or length, severe underweight, severe wasting and leucocytosis on admission. At discharge, cases had lower potassium levels and a higher proportion had persistent hypokalaemia. Cases received longer treatment with ampicillin and micronutrients. After adjusting for confounders, hypokalaemia was independently associated with poor socio-economic status, diarrhoea, lower pulse rates, hypocalcaemia, metabolic acidosis and leucocytosis. CONCLUSION: Identifying simple clinical signs, like diarrhoea and lower pulse rates, and laboratory parameters, such as hypocalcaemia and metabolic acidosis, may enable the early management of hypokalaemia in severely malnourished children under 5 years. This could reduce morbidity and mortality.

Strengthening the role of community health workers in supporting the recovery of ill, undernourished children post hospital discharge: qualitative insights from key stakeholders in Bangladesh and Kenya.

BACKGROUND: Undernourished children in low- and middle-income countries remain at elevated risk of death following hospital discharge, even when treated during hospitalisation using World Health Organisation recommended guidelines. The role of community health workers (CHWs) in supporting post-discharge recovery to improve outcomes has not been adequately explored. METHODS: This paper draws on qualitative research conducted as part of the Childhood Acute Illnesses and Nutrition (CHAIN) Network in Bangladesh and Kenya. We interviewed family members of 64 acutely ill children admitted across four hospitals (a rural and urban hospital in each country). 27 children had severe wasting or kwashiorkor on admission. Family members were interviewed in their homes soon after discharge, and up to three further times over the following six to fourteen months. These data were supplemented by observations in facilities and homes, key informant interviews with CHWs and policy makers, and a review of relevant guidelines. RESULTS: Guidelines suggest that CHWs could play a role in supporting recovery of undernourished children post-discharge, but the mechanisms to link CHWs into post-discharge support processes are not specified. Few families we interviewed reported any interactions with CHWs post-discharge, especially in Kenya, despite our data suggesting that opportunities for CHWs to assist families post-discharge include providing context sensitive information and education, identification of danger signs, and supporting linkages with community-based services and interventions. Although CHWs are generally present in communities, challenges they face in conducting their roles include unmanageable workloads, few incentives, lack of equipment and supplies and inadequate support from supervisors and some community members. CONCLUSION: A multi-pronged approach before or on discharge is needed to strengthen linkages between CHWs and children vulnerable to poor outcomes, supported by clear guidance. To encourage scale-ability and cost-effectiveness of interventions, the most vulnerable, high-risk children, should be targeted, including undernourished children. Intervention designs must also take into account existing health worker shortages and training levels, including for CHWs, and how any new tasks or personnel are incorporated into hospital and broader health system hierarchies and systems. Any such interventions will need to be evaluated in carefully designed studies, including tracking for unintended consequences.

Changing trends in measles vaccination status between 2004 and 2014 among children aged 12-23 months in Bangladesh.

OBJECTIVE: To assess the current measles vaccination status in Bangladesh, explain changing differentials in measles vaccination, and determine contexts that may improve measles vaccination coverage. METHODS: Secondary data analysis of datasets (2004-2014) from the nationally representative Bangladesh Demographic and Health Surveys that followed stratified, multi-stage cluster sampling design conducted both in urban and rural contexts. RESULTS: 5468 children aged 12-23 months were surveyed, of whom 892 (16%) reported non-compliance to measles vaccine. After simultaneous adjusting for covariates in multivariate logistic regression, children who came from a poor socio-economic background, who had mothers with no formal schooling, who were underweight, of higher birth order (≥4), who had adolescent mothers, who had a history of home delivery and who had no exposure to media were observed to be significantly associated with lack of measles vaccination. Measles vaccination coverage among children of adolescent mothers was consistently low. Despite lack of media exposure, measles vaccination status gradually increased from 26% in 2004 to 33% in 2014. Lack of maternal education was no longer associated with measles vaccination status in 2007, 2011 and 2014. Stunted children continued to be associated with lack of measles immunisation in 2014. Children with higher birth order demonstrated 53% excess risk for not being immunised with measles vaccine. Mothers with no exposure to mass media were two times more likely to have children without measles immunisation as indicated by BDHS 2014 data. CONCLUSIONS: Our findings will help policy makers formulate strategies for expanding measles vaccination coverage in order to achieve further reduction in disease burden and mortality in Bangladesh.

OBJECTIF: Evaluer l'état actuel de la vaccination antirougeoleuse au Bangladesh, expliquer l'évolution des écarts de vaccination antirougeoleuse et déterminer les contextes susceptibles d'améliorer la couverture vaccinale antirougeoleuse. MÉTHODES: Analyse des données secondaires des ensembles de données (2004 à 2014) des enquêtes démographiques et sanitaires du Bangladesh représentatives au niveau national, qui ont suivi un plan d'échantillonnage stratifié en grappes à plusieurs niveaux, mené à la fois dans des contextes urbains et ruraux. RÉSULTATS: 5.468 enfants de 12 à 23 mois ont été interrogés, dont 892 (16%) ont déclaré une non-adhésion au vaccin contre la rougeole. Après ajustement simultané des covariables dans la régression logistique multivariée, les enfants issus d'un milieu socioéconomique pauvre, dont les mères n'avaient pas de scolarité formelle, qui étaient en insuffisance pondérale, de rang de naissance supérieur (≥4), qui avaient des mères adolescentes, qui avaient un les antécédents d'accouchement à domicile et qui n'avaient pas été exposés aux médias étaient significativement associés à l'absence de vaccination contre la rougeole. La couverture vaccinale contre la rougeole chez les enfants de mères adolescentes était constamment faible. Malgré le manque d'exposition aux médias, le statut de vaccination contre la rougeole a progressivement augmenté, passant de 26% en 2004 à 33% en 2014. Le manque d'éducation maternelle n'était plus associé au statut de vaccination contre la rougeole en 2007, 2011 et 2014. Les enfants souffrant d'un retard de croissance ont continué d'être associés au manque de la vaccination contre la rougeole en 2014. Les enfants dont le rang de naissance était plus élevé ont démontré un risque de 53% en excès de ne pas être vacciné contre la rougeole. Les mères sans exposition aux médias de masse étaient deux fois plus susceptibles d'avoir des enfants sans vaccination contre la rougeole, comme l'indiquent les données BDHS 2014. CONCLUSIONS: Nos résultats aideront les décideurs à formuler des stratégies pour étendre la couverture vaccinale contre la rougeole afin de réduire encore la charge de morbidité et la mortalité au Bangladesh.

Pathogen-specific risk of seizure in children with moderate-to-severe diarrhoea: Case control study with follow-up.

OBJECTIVE: To determine the pathogen-specific risk of seizure in under-five children hospitalised with moderate-to-severe diarrhoea (MSD) in rural settings. METHOD: This was a prospective case-control study with follow-up, conducted in a sentinel facility of Global Enteric Multicenter Study in Mirzapur, a rural community of Bangladesh between 2007 and 2010. Children aged 0-59 months who presented with MSD and seizure constituted the cases whereas those who did not have seizure comprised the controls. MSD was defined if the episodes were associated with dehydration or dysentery or required hospitalisation with diarrhoea or dysentery. All enrolled children were followed up at home within 50-90 days of enrolment. A total of 64 cases and 128 randomly selected controls formed the analysable dataset. RESULTS: The result of logistic regression analysis after adjusting for potential confounders revealed that shigellosis (Shigella species, OR = 5.34, 95% CI = 2.37-12.04) particularly S. flexneri (OR = 3.34, 95% CI = 1.48-7.57), S. flexneri 6 (OR = 23.24, 95% CI = 2.79-193.85), S. sonnei (OR = 6.90, 95% CI = 2.34-19.85); norovirus (OR = 6.77, 95% CI = 1.69-27.11), fever (OR = 16.75, 95% CI = 1.81-154.70) and loss of consciousness (OR = 35.25, 95% CI = 1.71-726.20) were the independent risk factors for seizure in MSD children. At enrolment, cases had lower WHZ (P = 0.006) compared to their peers, follow-up anthropometrics showed significant improvement in WHZ (P < 0.001) and WAZ (P < 0.05), whereas deterioration in HAZ (P < 0.001) in both cases and controls. CONCLUSION: Childhood MSD episodes particularly due to Shigella and norovirus are often associated with seizure. Prompt identification and appropriate management of children with shigellosis may reduce occurrence and adverse consequences of seizure linked with MSD.

OBJECTIF: Déterminer le risque spécifique de convulsions chez les enfants de moins de cinq ans hospitalisés pour une diarrhée modérée à sévère (DMS) en milieu rural. MÉTHODE: Il s'agissait d'une étude prospective cas-témoins avec suivi, menée dans un établissement sentinelle de l'Etude Globale Multicentrique Entérique à Mirzapur, une communauté rurale du Bangladesh entre 2007 et 2010. Les enfants âgés de 0 à 59 mois qui se sont présentés avec une DMS et des convulsions constituaient les cas, tandis que ceux qui n'avaient pas des convulsions constituaient les témoins. La DMS a été définie si les épisodes étaient associés à une déshydratation ou à une dysenterie ou nécessitaient une hospitalisation pour diarrhée ou dysenterie. Tous les enfants recrutés ont été suivis à domicile dans les 50 à 90 jours suivant le recrutement. Un total de 64 cas et 128 témoins sélectionnés au hasard ont constitué l'ensemble de données analysables. RÉSULTATS: Le résultat de l'analyse de régression logistique après ajustement des facteurs de confusion potentiels a révélé que la shigellose (espèce Shigella, OR = 5,34 ; IC95%: 2,37-12,04) en particulier S. flexneri (OR = 3,34 ; IC95%: 1,48-7,57), S. flexneri 6 (OR = 23,24 ; IC95%: 2.79-193,85), S. sonnei (OR = 6,90 ; IC95%: 2,34-19,85) ; les norovirus (OR = 6,77 ; IC95%: 1,69-27,11), la fièvre (OR = 16,75 ; IC95%: 1,81-154,70) et la perte de conscience (OR = 35,25 ; IC95%: 1,71-726,20) étaient les facteurs de risque indépendants de convulsions chez les enfants souffrant de DMS. Lors du recrutement, les cas avaient un score Z poids pour la taille (ZPT) plus faible (P = 0,006) que leurs pairs, les anthropométries de suivi ont montré une amélioration significative du ZPT (P < 0,001) et du score Z poids pour l'âge (P < 0,05); tandis que le score Z taille pour l'âge (p < 0,001) s'est détérioré chez cas et chez les témoins. CONCLUSION: Les épisodes de DMS de l'enfance, notamment due à Shigella et aux norovirus, sont souvent associés à des convulsions. L'identification rapide et la prise en charge appropriée des enfants atteints de shigellose peuvent réduire la survenue et les conséquences négatives des crises liées aux DMS.

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.

COVID-19 PICU guidelines: for high- and limited-resource settings.

BACKGROUND: Fewer children than adults have been affected by the COVID-19 pandemic, and the clinical manifestations are distinct from those of adults. Some children particularly those with acute or chronic co-morbidities are likely to develop critical illness. Recently, a multisystem inflammatory syndrome (MIS-C) has been described in children with some of these patients requiring care in the pediatric ICU. METHODS: An international collaboration was formed to review the available evidence and develop evidence-based guidelines for the care of critically ill children with SARS-CoV-2 infection. Where the evidence was lacking, those gaps were replaced with consensus-based guidelines. RESULTS: This process has generated 44 recommendations related to pediatric COVID-19 patients presenting with respiratory distress or failure, sepsis or septic shock, cardiopulmonary arrest, MIS-C, those requiring adjuvant therapies, or ECMO. Evidence to explain the milder disease patterns in children and the potential to use repurposed anti-viral drugs, anti-inflammatory or anti-thrombotic therapies are also described. CONCLUSION: Brief summaries of pediatric SARS-CoV-2 infection in different regions of the world are included since few registries are capturing this data globally. These guidelines seek to harmonize the standards and strategies for intensive care that critically ill children with COVID-19 receive across the world. IMPACT: At the time of publication, this is the latest evidence for managing critically ill children infected with SARS-CoV-2. Referring to these guidelines can decrease the morbidity and potentially the mortality of children effected by COVID-19 and its sequalae. These guidelines can be adapted to both high- and limited-resource settings.

Continuing professional education for general practitioners on chronic obstructive pulmonary disease: feasibility of a blended learning approach in Bangladesh.

BACKGROUND: Continuing medical education (CME) is essential to developing and maintaining high quality primary care. Traditionally, CME is delivered face-to-face, but due to geographical distances, and pressure of work in Bangladesh, general practitioners (GPs) are unable to relocate for several days to attend training. Using chronic obstructive pulmonary disease (COPD) as an exemplar, we aimed to assess the feasibility of blended learning (combination of face-to-face and online) for GPs, and explore trainees' and trainers' perspectives towards the blended learning approach. METHODS: We used a mixed-methods design. We trained 49 GPs in two groups via blended (n = 25) and traditional face-to-face approach (n = 24) and assessed their post-course knowledge and skills. The COPD Physician Practice Assessment Questionnaire (COPD-PPAQ) was administered before and one-month post-course. Verbatim transcriptions of focus group discussions with 18 course attendees and interviews with three course trainers were translated into English and analysed thematically. RESULTS: Forty GPs completed the course (Blended: 19; Traditional: 21). The knowledge and skills post course, and the improvement in self-reported adherence to COPD guidelines was similar in both groups. Most participants preferred blended learning as it was more convenient than taking time out of their busy work life, and for many the online learning optimised the benefits of the subsequent face-to-face sessions. Suggested improvements included online interactivity with tutors, improved user friendliness of the e-learning platform, and timing face-to-face classes over weekends to avoid time-out of practice. CONCLUSIONS: Quality improvement requires a multifaceted approach, but adequate knowledge and skills are core components. Blended learning is feasible and, with a few caveats, is an acceptable option to GPs in Bangladesh. This is timely, given that online learning with limited face-to-face contact is likely to become the norm in the on-going COVID-19 pandemic.

Awareness Development and Usage of Mobile Health Technology Among Individuals With Hypertension in a Rural Community of Bangladesh: Randomized Controlled Trial.

BACKGROUND: Hypertension (HTN) is a major modifiable risk factor and the leading cause of premature deaths globally. The lack of awareness and knowledge have been identified as risk factors in low- and middle-income countries including Bangladesh. Recently, the use of mobile phone SMS text messaging is found to have an important positive impact on HTN management. OBJECTIVE: The study aimed to develop awareness and knowledge in order to enhance lifestyle behavior changes among individuals with HTN in a rural community of Bangladesh by using health education and mobile health (mHealth) technology (SMS text messaging). METHODS: A prospective randomized 5-month intervention, open-label (1:1), parallel-group trial was implemented among the individuals with HTN aged 35 years or older. Both men and women were included. Between August 2018 and July 2019, we enrolled 420 participants, selected from a tertiary level health facility and through door-to-door visits by community health workers. After block randomization, they were assigned to either the intervention group (received SMS text messaging and health education; n=209) or the control group (received only health education; n=211). The primary outcome was the evaluation of self-reported behavior changes (salt intake, fruits and vegetables intake, physical activity, and blood pressure [BP], and body weight monitoring behaviors). The secondary outcomes were measurements of actual salt intake and dietary salt excretion, blood glucose level, BP values, and quality of life (QOL). RESULTS: During the study period, a total of 8 participants were dropped, and the completion rate was 98.0% (412/420). The adherence rates were significantly higher (9%) among the control group regarding salt intake (P=.04) and physical activity behaviors (P<.03), and little differences were observed in other behaviors. In primary outcome, the focused behavior, salt intake less than 6 g/day, showed significant chronological improvement in both groups (P<.001). The fruits intake behavior steadily improved in both groups (P<.001). Participants in both groups had a custom of vegetables intake everyday/week. Physical activity suddenly increased and continued until the study end (P<.001 in both groups). Both BP and body weight monitoring status increased from baseline to 1 month but decreased afterward (P<.001). In case of secondary outcomes, significant chronological changes were observed in food salt concentration and urinary salinity between the groups (P=.01). The mean systolic BP and diastolic BP significantly chronologically decreased in both groups (systolic BP, P=.04; diastolic BP, P=.02.P<.05). All of these supported self-reported behavior changes. For the QOL, both groups showed significant improvement over the study periods (P<.001). CONCLUSIONS: Based on these results, we suggest that face-to-face health education requires integration of home health care provision and more relevant and timely interactive SMS text messages to increase the effectiveness of the intervention. Besides, community awareness can be created to encourage "low-salt culture" and educate family members. TRIAL REGISTRATION: Bangladesh Medical Research Council (BMRC) 06025072017; ClinicalTrials.gov NCT03614104; https://clinicaltrials.gov/ct2/show/NCT03614104 and UMIN-CTR R000033736; https://tinyurl.com/y48yfcoo. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/15523.

Efficacy of High-Flow Nasal Cannula vs Standard Oxygen Therapy or Nasal Continuous Positive Airway Pressure in Children with Respiratory Distress: A Meta-Analysis.

OBJECTIVES: To evaluate the efficacy of high-flow nasal cannula (HFNC) oxygen therapy in providing respiratory support of children with acute lower respiratory infection (ALRI), hypoxemia, and respiratory distress. STUDY DESIGN: We performed a meta-analysis of randomized controlled trials that compared HFNC and standard flow oxygen therapy or nasal continuous positive airway pressure (nCPAP) and reported treatment failure as an outcome. Data were synthesized using Mann-Whitney U test. RESULTS: Compared with standard oxygen therapy, HFNC significantly reduced treatment failure (risk ratio [RR] 0.49, 95% CI 0.40-0.60, P < .001) in children with mild hypoxemia (arterial pulse oximetry [SpO2] >90% on room air). HFNC had an increased risk of treatment failure compared with nCPAP in infants age 1-6 months with severe hypoxemia (SpO2 <90% on room air or SpO2 >90% on supplemental oxygen) (RR 1.77, 95% CI 1.17-2.67, P = .007). No significant differences were found in intubation rates and mortality between HFNC and standard oxygen therapy or nCPAP. HFNC had a lower risk of nasal trauma compared with nCPAP (RR 0.35, 95% CI 0.16-0.77, P = .009). CONCLUSIONS: Among children <5 years of age with ALRI, respiratory distress, and mild hypoxemia, HFNC reduced the risk of treatment failure when compared with standard oxygen therapy. However, nCPAP was associated with a lower risk of treatment failure than HFNC in infants age 1-6 months with ALRI, moderate-to-severe respiratory distress, and severe hypoxemia. No differences were found in intubation and mortality between HFNC and standard oxygen therapy or nCPAP.

Health seeking behaviour and delayed management of tuberculosis patients in rural Bangladesh.

BACKGROUND: Early diagnosis of tuberculosis (TB) and involvement of the public-private partnership are critical to eradicate TB. Patients need to receive proper treatment through the National Tuberculosis Control Programme (NTP). This study describes various predictors for health seeking behaviour of TB patients and health system delay made by the different health care providers. METHODS: A cross-sectional study was conducted in a public health facility of a rural area in Bangladesh. Newly diagnosed smear positive pulmonary TB (PTB) patients who were ≥ 15 years of age were sequentially enrolled in this study. The socio-demographic characteristics and proportion of health care utilization by the patients, and health system delay made by the health care providers were calculated. Multivariate analysis was conducted to determine the independent association of the risk factors with the time to seek medical care. RESULTS: Two hundred and eighty patients were enrolled in this study. Among them, 73.6% were male and 26.4% were female. A hundred percent of patients primarily sought treatment for their cough, 170 (60.7%) first consulted a non-qualified practitioner while 110 patients (39.3%) first consulted with qualified practitioners about their symptoms. Pharmacy contact was the highest (27.9%) among the non-qualified practitioners, and 58.9% non-qualified practitioners prescribed treatment without any laboratory investigation. The average health system delay was 68.5 days. Multiple logistic regressions revealed a significant difference between uneducated and educated patients (OR 2.33; CI 1.39-3.92), and qualified and non-qualified practitioners (OR 2.34; CI 1.38-3.96) to be independent predictors of health system delay. CONCLUSIONS: Compared to men, fewer women sought TB treatment. Uneducated patients and questionably qualified practitioners made for a longer delay in detecting TB. Increasing public health awareness and improving health seeking behavior of females and uneducated patients, and greater participation of the qualified practitioners in the NTP are highly recommended.

Effectiveness of an educational intervention to improve antibiotic dispensing practices for acute respiratory illness among drug sellers in pharmacies, a pilot study in Bangladesh.

BACKGROUND: Inappropriate dispensing of antibiotics for acute respiratory illness (ARI) is common among drug sellers in Bangladesh. In this study, we evaluated the impact of an educational intervention to promote guidelines for better ARI management among drug sellers. METHODS: From June 2012 to December 2013, we conducted baseline and post-intervention surveys on dispensing practices in 100 pharmacies within Dhaka city. In these surveys, drug sellers participated in 6 standardized role-playing scenarios led by study staffs acting as caregivers of ARI patients and drug sellers were blinded to these surveys. After the baseline survey, we developed ARI guidelines and facilitated a one-day educational intervention about ARI management for drug sellers. Our guidelines only recommended antibiotics for children with complicated ARI. Finally, we conducted the six month post-intervention survey using the same scenarios to record changes in drug dispensing practices. RESULTS: Only 2/3 of participating pharmacies were licensed and few (11%) of drug sellers had pharmacy training. All the drug sellers were male, had a median age of 34 years (IQR 28-41). For children, dispensing of antibiotics for uncomplicated ARI decreased (30% baseline vs. 21% post-intervention; p = 0.04), but drug sellers were equally likely to dispense antibiotics for complicated ARI (15% baseline vs. 17% post-intervention; p = 0.6) and referrals to physicians for complicated ARIs decreased (70% baseline vs. 58% post-intervention; p = 0.03). For adults, antibiotic dispensing remained similar for uncomplicated ARI (48% baseline vs. 40% post-intervention; p = 0.1) but increased among those with complicated ARI (44% baseline vs. 78% post-intervention; p < 0.001). Although our evidence-based guidelines recommended against prescribing antihistamines for children, drug sellers continued to sell similar amounts for uncomplicated ARI (33% baseline vs. 32% post-intervention; p = 0.9). CONCLUSIONS: Despite the intervention, drug sellers continued to frequently dispense antibiotics for ARI, except for children with uncomplicated ARI. Pairing educational interventions among drug sellers with raising awareness about proper antibiotic use among general population should be further explored. In addition, annual licensing and an reaccreditation system with comprehensive monitoring should be enforced, using penalties for non-compliant pharmacies as possible incentives for appropriate dispensing practices.