Implementation of bubble continuous positive airway pressure for children with severe pneumonia and hypoxemia in intensive care unit of Dhaka Hospital, Bangladesh-Effect on pneumonia mortality.

BACKGROUND: After the completion of a randomized trial at Dhaka Hospital in 2013, bubble continuous positive airway pressure (BCPAP) oxygen therapy was incorporated as the part of the standard treatment for children with severe pneumonia with hypoxemia in an intensive care unit at Dhaka Hospital in August 2013 instead of World Health Organization (WHO) standard low flow oxygen therapy. OBJECTIVE: To understand the long-term effectiveness of the introduction of bCPAP oxygen therapy by comparing pneumonia mortality in the post-trial period (August 2013 to December 2017) with the pre-trial (February 2009 to July 2011) and trial periods (August 2011 to July 2013). METHODS: It was a retrospective analysis of prospectively collected hospital data of all admissions. Mortality rates of all children with WHO-defined pneumonia, and the subset of children with severe pneumonia and hypoxemia (oxygen saturation <90%) were evaluated. RESULTS: The analysis covered 10,107 children with pneumonia: 2523 in the pre-trial (414 with severe pneumonia and hypoxemia; none of them received bCPAP), 2959 during the trial (376 with severe pneumonia and hypoxemia; 79 received bCPAP), and 4625 in the post-trial period (1208 with severe pneumonia and hypoxemia; 1125 had bCPAP). The risk of death from pneumonia in the post-trial period was lower than in pre-trial (adjusted risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58-0.92; p = 0.007), among children with severe pneumonia and hypoxemia, the risk of death was lower in the post-trial period than in the pre-trial (adjusted RR = 0.46, 95% CI = 0.37-0.58, p < 0.001), and the trial period (adjusted RR = 0.70, 95% CI = 0.51-0.95; p = 0.023). CONCLUSION: After the introduction of bCPAP oxygen therapy as part of the routine management of severe pneumonia and hypoxemia in the ICU of the Dhaka hospital, we observed significantly lower mortality, even after accounting for measurable confounding.

The Role of Food Insecurity and Dietary Diversity on Recovery from Wasting among Hospitalized Children Aged 6-23 Months in Sub-Saharan Africa and South Asia.

Background: Current guidelines for the management of childhood wasting primarily focus on the provision of therapeutic foods and the treatment of medical complications. However, many children with wasting live in food-secure households, and multiple studies have demonstrated that the etiology of wasting is complex, including social, nutritional, and biological causes. We evaluated the contribution of household food insecurity, dietary diversity, and the consumption of specific food groups to the time to recovery from wasting after hospital discharge. Methods: We conducted a secondary analysis of the Childhood Acute Illness Network (CHAIN) cohort, a multicenter prospective study conducted in six low- or lower-middle-income countries. We included children aged 6−23 months with wasting (mid-upper arm circumference [MUAC] ≤ 12.5 cm) or kwashiorkor (bipedal edema) at the time of hospital discharge. The primary outcome was time to nutritional recovery, defined as a MUAC > 12.5 cm without edema. Using Cox proportional hazards models adjusted for age, sex, study site, HIV status, duration of hospitalization, enrollment MUAC, referral to a nutritional program, caregiver education, caregiver depression, the season of enrollment, residence, and household wealth status, we evaluated the role of reported food insecurity, dietary diversity, and specific food groups prior to hospitalization on time to recovery from wasting during the 6 months of posthospital discharge. Findings: Of 1286 included children, most participants (806, 63%) came from food-insecure households, including 170 (13%) with severe food insecurity, and 664 (52%) participants had insufficient dietary diversity. The median time to recovery was 96 days (18/100 child-months (95% CI: 17.0, 19.0)). Moderate (aHR 1.17 [0.96, 1.43]) and severe food insecurity (aHR 1.14 [0.88, 1.48]), and insufficient dietary diversity (aHR 1.07 [0.91, 1.25]) were not significantly associated with time to recovery. Children who had consumed legumes and nuts prior to diagnosis had a quicker recovery than those who did not (adjusted hazard ratio (aHR): 1.21 [1.01,1.44]). Consumption of dairy products (aHR 1.13 [0.96, 1.34], p = 0.14) and meat (aHR 1.11 [0.93, 1.33]), p = 0.23) were not statistically significantly associated with time to recovery. Consumption of fruits and vegetables (aHR 0.78 [0.65,0.94]) and breastfeeding (aHR 0.84 [0.71, 0.99]) before diagnosis were associated with longer time to recovery. Conclusion: Among wasted children discharged from hospital and managed in compliance with wasting guidelines, food insecurity and dietary diversity were not major determinants of recovery.

Antibiotic-Resistant Bacteremia in Young Children Hospitalized With Pneumonia in Bangladesh Is Associated With a High Mortality Rate.

BACKGROUND: Pneumonia is a leading cause of sepsis and mortality in children under 5 years. However, our understanding of the causes of bacteremia in children with pneumonia is limited. METHODS: We characterized risk factors for bacteremia and death in a cohort of children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between 2014 and 2017 with radiographically confirmed pneumonia. RESULTS: A total of 4007 young children were hospitalized with pneumonia over the study period. A total of 1814 (45%) had blood cultures obtained. Of those, 108 (6%) were positive. Gram-negative pathogens predominated, accounting for 83 (77%) of positive cultures. These included Pseudomonas (N = 22), Escherichia coli (N = 17), Salmonella enterica (N = 14, including 11 Salmonella Typhi), and Klebsiella pneumoniae (N = 11). Gram-positive pathogens included Pneumococcus (N = 7) and Staphylococcus aureus (N = 6). Resistance to all routinely used empiric antibiotics (ampicillin, gentamicin, ciprofloxacin, and ceftriaxone) for children with pneumonia at the icddr,b was observed in 20 of the 108 isolates. Thirty-one of 108 (29%) children with bacteremia died, compared to 124 of 1706 (7%) who underwent culture without bacteremia (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3-8.1; P < .001). Children infected with bacteria resistant to all routinely used empiric antibiotics were at greater risk of death compared to children without bacteremia (OR, 17.3; 95% CI, 7.0-43.1; P < .001). CONCLUSIONS: Antibiotic-resistant Gram-negative bacteremia in young children with pneumonia in Dhaka, Bangladesh was associated with a high mortality rate. The pandemic of antibiotic resistance is shortening the lives of young children in Bangladesh, and new approaches to prevent and treat these infections are desperately needed.

Clinical and laboratory predictors of 30-day mortality in severe acute malnourished children with severe pneumonia.

OBJECTIVE: To determine the predictors of mortality within 30 days of hospital admission in a diarrhoeal disease hospital in Bangladesh. METHODS: Cohort study of hospitalised children aged 0-59 months with severe acute malnutrition (SAM) and severe pneumonia in Dhaka Hospital, icddr,b, Bangladesh from April 2015 to March 2017. Those discharged were followed up, and survival status at 30 days from admission was determined. Children who died were compared with the survivors in terms of clinical and laboratory biomarkers. Multivariable logistic regression analysis was used for calculating adjusted odds ratio for death within 30 days of hospital admission. RESULTS: We enrolled 191 children. Mortality within 30 days of admission was 6% (14/191). After adjusting for potential confounders (hypoxia, CRP and haematocrit) in logistic regression analysis, independent factors associated with death were female sex (aOR = 5.80, 95% CI: 1.34-25.19), LAZ <-4 (aOR = 6.51, 95% CI: 1.49-28.44) and Polymorphonuclear Leucocytes (PMNL) (>6.0 × 109 /L) (aOR = 1.06, 95% CI: 1.01-1.11). Using sex, Z-score for length for age (LAZ), and PMNL percentage, we used random forest and linear regression models to achieve a cross-validated AUC of 0.83 (95% CI: 0.82, 0.84) for prediction of 30-day mortality. CONCLUSIONS: The results of our data suggest that female sex, severe malnutrition (<-4 LAZ) and higher PMNL percentage were prone to be associated with 30-day mortality in children with severe pneumonia. Association of these factors may be used in clinical decision support for prompt identification and appropriate management for prevention of mortality in this population.

OBJECTIF: Déterminer les prédicteurs de mortalité dans les 30 jours suivant l'admission à l'hôpital dans un hôpital pour maladies diarrhéiques au Bangladesh. MÉTHODES: Etude de cohorte d'enfants hospitalisés âgés de 0 à 59 mois atteints de malnutrition aiguë sévère (MAS) et de pneumonie sévère à l'hôpital de Dhaka, icddr,b, au Bangladesh d'avril 2015 à mars 2017. Ceux qui ont été libérés ont été suivis et leur état de survie à 30 jours de l'admission a été déterminé. Les enfants décédés ont été comparés aux survivants en termes de biomarqueurs cliniques et de laboratoire. Une analyse de régression logistique multivariée a été utilisée pour calculer le rapport de cotes ajusté pour le décès dans les 30 jours suivant l'admission à l'hôpital. RÉSULTATS: Nous avons inscrit 191 enfants. La mortalité dans les 30 jours suivant l'admission était de 6% (14/191). Après ajustement pour les facteurs confusionnels potentiels (hypoxie, CRP et hématocrite) dans l'analyse de régression logistique, les facteurs indépendants associés au décès étaient le sexe féminin (aOR = 5,80 ; IC95%: 1,34 à 25,19), LAZ <-4 (aOR = 6,51 ; IC95%: 1,49-28,44) et leucocytes polymorphonucléaires (LPMN) (>6,0 x 109 /L) (aOR = 1,06 ; IC95%: 1,01-1,11). En utilisant le sexe, le score Z de la taille pour l'âge (LAZ) et le pourcentage de LPMN, nous avons utilisé des modèles de régression linéaire et de forest aléatoires pour obtenir une AUC validée croisée de 0,83 (IC95%: 0,82-0,84) pour la prédiction de la mortalité à 30 jours. CONCLUSIONS: Les résultats de nos données suggèrent que le sexe féminin, la malnutrition sévère (LAZ <-4) et un pourcentage plus élevé de LPMN étaient susceptibles d'être associés à la mortalité à 30 jours chez les enfants atteints de pneumonie sévère. L'association de ces facteurs peut être utilisée dans l'aide à la décision clinique pour une identification rapide et une prise en charge appropriée pour la prévention de la mortalité dans cette population.

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.

Comparative Performance of Modified Kenneth Jones Criteria Scoring, World Health Organization Criteria, and Antibodies in Lymphocyte Supernatant for Diagnosing Tuberculosis in Severely Malnourished Children Presenting With Pneumonia.

Background: The diagnosis of childhood tuberculosis (TB) can be difficult in severely malnourished children. This is mainly due to the fact of our perceived notion that clinical signs of TB are often subtle in severely malnourished children and we may rely on laboratory investigation for the diagnosis. However, comparative data on the performance of clinical and laboratory diagnostics of TB in such population are also very limited. Objectives: To compare the performance of composite clinical criteria and a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children with pneumonia. Methods: Severely malnourished children under five with radiological pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh were enrolled consecutively following informed consent. We collected venous blood for ALS, gastric lavage fluid and induced sputum for microscopy, mycobacterial culture, and real-time PCR by Xpert MTB/RIF. We compared the sensitivity, specificity, positive, and negative predictive values, and accuracy of modified Kenneth Jones criteria (MKJC) score, World Health Organization (WHO) criteria, and ALS in diagnosing TB in severely malnourished children with pneumonia for "Confirmed TB" and "All TB" ("Confirmed TB" plus "Probable TB") vs. "Not TB." Results: Compared to culture confirmed TB, the sensitivity, and specificity (95% CI) for MKJC were 60 (27-86) and 84 (79-87)% and for WHO criteria were 40 (14-73) and 84 (80-87)%, respectively. Compared to culture and/or Xpert MTB/RIF positive TB, the sensitivity and specificity (95% CI) for the criteria were 37 (20-58) and 84 (79-87)%; and 22 (9-43) and 83 (79-87)%, respectively. For both these comparisons, the sensitivity and specificity of ALS were 50 (14-86) and 60 (53-67)%, respectively. Conclusion: Our data suggest that WHO criteria and MKJC scoring mainly based on clinical criteria are more useful than ALS in diagnosing TB in young severely malnourished children with pneumonia. The results underscore the importance of using clinical criteria for the diagnosis of TB in severely malnourished children that may help to minimize the chance of over treatment with anti-TB in such population, especially in resource limited TB endemic settings.

Consequences of Lack of Neonatal Breastfeeding in Infants Hospitalized for Diarrhea at an Urban Hospital, Bangladesh: A Case Control Design.

Background. Exclusive breastfeeding is important for immunity and lack of breastfeeding during the neonatal age impedes that. Our aim was to assess the consequences of lack of breastfeeding on infants with diarrhea in the neonatal period. Methods. In this design, infants from DDSS (Diarrheal Disease Surveillance System) from 2009 to 2013 were studied. Those who did not have breastfeeding or had cessation of breastfeeding at the neonatal age constituted the cases, whereas infants who continued breastfeeding since birth or for at least 6 months since birth constituted the controls. Results. The cases more often presented at a younger age, had an illiterate mother, frequently presented with complicated diarrhea, had severe wasting, and had abnormal mental status compared with the controls. In logistic regression, after adjusting for potential confounders, infants who lacked breastfeeding at the neonatal period had an independent association with dehydrating diarrhea. Conclusions. The results of our analyses suggest that infants with diarrhea who did not have breastfeeding at the neonatal age are prone to develop some or severe dehydration.

A mixed method multi-country assessment of barriers to implementing pediatric inpatient care guidelines.

INTRODUCTION: Accelerating progress in reducing child deaths is needed in order to achieve the Sustainable Development Goal child mortality target. This will require a focus on vulnerable children-including young children, those who are undernourished or with acute illnesses requiring hospitalization. Improving adherence to inpatient guidelines may be an important strategy to reduce child mortality, including among the most vulnerable. The aim of our assessment of nine sub-Saharan African and South Asian hospitals was to determine adherence to pediatric inpatient care recommendations, in addition to capacity for and barriers to implementation of guideline-adherent care prior to commencing the Childhood Acute Illness and Nutrition (CHAIN) Cohort study. The CHAIN Cohort study aims to identify modifiable risk factors for poor inpatient and post discharge outcomes above and beyond implementation of guidelines. METHODS: Hospital infrastructure, staffing, durable equipment, and consumable supplies such as medicines and laboratory reagents, were evaluated through observation and key informant interviews. Inpatient medical records of 2-23 month old children were assessed for adherence to national and international guidelines. The records of children with severe acute malnutrition (SAM) were oversampled to reflect the CHAIN study population. Seven core adherence indicators were examined: oximetry and oxygen therapy, fluids, anemia diagnosis and transfusion, antibiotics, malaria testing and antimalarials, nutritional assessment and management, and HIV testing. RESULTS: All sites had facilities and equipment necessary to implement care consistent with World Health Organization and national guidelines. However, stockouts of essential medicines and laboratory reagents were reported to be common at some sites, even though they were mostly present during the assessment visits. Doctor and nurse to patient ratios varied widely. We reviewed the notes of 261 children with admission diagnoses of sepsis (17), malaria (47), pneumonia (70), diarrhea (106), and SAM (119); 115 had multiple diagnoses. Adherence to oxygen therapy, antimalarial, and malnutrition refeeding guidelines was >75%. Appropriate antimicrobials were prescribed for 75% of antibiotic-indicative conditions. However, 20/23 (87%) diarrhea and 20/27 (74%) malaria cases without a documented indication were prescribed antibiotics. Only 23/122 (19%) with hemoglobin levels meeting anemia criteria had recorded anemia diagnoses. HIV test results were infrequently documented even at hospitals with universal screening policies (66/173, 38%). Informants at all sites attributed inconsistent guideline implementation to inadequate staffing. CONCLUSION: Assessed hospitals had the infrastructure and equipment to implement guideline-consistent care. While fluids, appropriate antimalarials and antibiotics, and malnutrition refeeding adherence was comparable to published estimates from low- and high-resource settings, there were inconsistencies in implementation of some other recommendations. Stockouts of essential therapeutics and laboratory reagents were a noted barrier, but facility staff perceived inadequate human resources as the primary constraint to consistent guideline implementation.

Hyperkalemia Was an Independent Risk Factor for Death While Under Mechanical Ventilation Among Children Hospitalized With Diarrhea in Bangladesh.

Objectives. We sought to evaluate the admission and hospital risk factors for death in children with diarrhea requiring mechanical ventilation (MV). Methods. This was a retrospective study. We enrolled children aged 0 to 59 months admitted with diarrhea to the intensive care unit of the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between August 2009 and July 2013 and required MV. To evaluate the risk factors for death in MV, we compared the clinical and laboratory characteristics of the children requiring MV. We matched up to the clinical characteristics presented on admission and subsequently developed before MV during hospital stay with the survivors and deaths of children having MV. Results. Among 73 enrolled children, 58 (80%) died. Incidence of death in MV was higher among children having hyperkalemia (P ≤ .001), hypoglycemia (P ≤ .001), and metabolic acidosis (P = .06) on admission and lower in children having tracheal isolates (P ≤ .001) during hospitalization. After adjusting for covariates by using multivariate robust Poisson regression, children with hyperkalemia (incidence ratio = 1.34; P = .03; confidence interval = 1.02-1.76) on admission was the only independent risk factor for death of children with MV. Conclusion. Children with hyperkalemia on admission and subsequently requiring MV were more likely to die compared with those without hyperkalemia.

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

BACKGROUND: Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO). Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing. METHODS: This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) during January 2014 to December 2014 having age specific fast breathing (<2 month ≥60 breath/min, 2-11 months ≥50 breaths/min, >11-59 months ≥40 breaths/min) were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276) and those without pneumonia constituted the controls (n = 446). Comparison of clinical features and outcomes between the cases and the controls was made. RESULTS: The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12). The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23). In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; p<0.01) and chest wall indrawing (OR = 31.05, 95%CI = 13.43-71.82; p<0.01) and less often had severe acute malnutrition (OR = 0.33, 95%CI = 0.13-0.79; p<0.01). The sensitivity and specificity of cough were 83% (78-87%) and 93% (91-96%). The sensitivity and specificity for lower chest wall indrawing were 65% (59-71%) and 95% (93-97%). However, the sensitivity and specificity of cough and lower chest wall indrawing combined were 94% (89-97%) and 99% (97-100%). CONCLUSION AND SIGNIFICANCE: Thus, diarrheal children having fast breathing who present with cough and/or lower chest wall indrawing, irrespective of presence or absence of metabolic acidosis, are more likely to have radiological pneumonia. The results underscore the importance of early identification of these simple clinical features that may help to minimize potential delay due to rehydration in initiating prompt treatment of pneumonia in order to reduce fatal consequences in such children.

Hypoxaemia and septic shock were independent risk factors for mechanical ventilation in Bangladeshi children hospitalised for diarrhoea.

AIM: In Bangladesh, approximately 6% of children under five years of age die due to diarrhoea. We evaluated the admission and hospitalisation risk factors for mechanical ventilation and outcomes in children with diarrhoea. METHODS: This retrospective case-control chart analysis was conducted in the intensive care unit of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We enrolled 219 children with diarrhoea aged 0-59 months between August 2009 and July 2013. The 73 cases were children who were initially identified as requiring mechanical ventilation during the study period, and the 146 controls were randomly selected from those who did not require mechanical ventilation. We compared the groups to determine the risk factors for mechanical ventilation. RESULTS: Mortality was significantly higher among the cases than the controls (p < 0.001). In the logistic regression analysis carried out for two separate time points, the independent risk factors for mechanical ventilation on admission were hypoxaemia (p < 0.001) and septic shock (p = 0.004) and during hospitalisation, they were intake of intravenous fluid (p = 0.015), hypokalaemia (p = 0.018), hyperkalaemia (p = 0.005) and septic shock (p = 0.001). CONCLUSION: Children under five with diarrhoea who required mechanical ventilation frequently had hypoxaemia and septic shock and were more likely to die than unventilated controls.

Diagnosis of Tuberculosis Following World Health Organization-Recommended Criteria in Severely Malnourished Children Presenting With Pneumonia.

Evidences on diagnosis of tuberculosis (TB) following the World Health Organization (WHO) criteria in children with severe acute malnutrition (SAM) are lacking. We sought to evaluate the WHO criteria for the diagnosis of TB in such children. In this prospective study, we enrolled SAM children aged <5 with radiological pneumonia. We collected induced sputum and gastric lavage for smear microscopy, mycobacterial culture, and Xpert MTB/RIF. Using the last 2 methods as the gold standard, we determined sensitivity, specificity, and positive and negative predictive values of WHO criteria (n = 388). However, Xpert MTB/RIF was performed on the last 214 children. Compared to mycobacterial culture-confirmed TB, sensitivity and specificity (95% confidence interval) of WHO criteria were 40 (14% to 73%) and 84 (80% to 87%), respectively. Compared to culture- and/or Xpert MTB/RIF-confirmed TB, the values were 22% (9% to 43%) and 83 (79% to 87%), respectively. Thus, the good specificity of the WHO criteria may help minimize overtreatment with anti-TB therapy in SAM children, especially in resource-limited settings.

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

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

Impact of Diarrhea on the Clinical Presentation and Outcome of Severe Pneumonia in Bangladeshi Children.

We compared clinical presentation and outcome of 225 children with severe pneumonia between those with and those without diarrhea. Having diarrhea was associated with metabolic acidosis (P < 0.001) and hypocalcemia (P = 0.002) on presentation, and with a fatal outcome: 20/113 (20%) died with diarrhea versus 3/112 (3%) without diarrhea. Diarrhea is an important comorbidity in Bangladeshi children with severe pneumonia requiring attention for improved case management.

Treatment Failure and Mortality amongst Children with Severe Acute Malnutrition Presenting with Cough or Respiratory Difficulty and Radiological Pneumonia.

BACKGROUND: Appropriate intervention is critical in reducing deaths among under-five, severe acutely malnourished (SAM) children with danger signs of severe pneumonia; however, there is paucity of data on outcome of World Health Organisation (WHO) recommended interventions of SAM children with severe pneumonia. We sought to evaluate outcome of the interventions in such children. METHODS: We prospectively enrolled SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU) or Acute Respiratory Infection (ARI) ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), between April 2011 and June 2012 with cough or respiratory difficulty and radiological pneumonia. All the enrolled children were treated with ampicillin and gentamicin, and micronutrients as recommended by the WHO. Comparison was made among pneumonic children with (n = 111) and without WHO defined danger signs of severe pneumonia (n = 296). The outcomes of interest were treatment failure (if a child required changing of antibiotics) and deaths during hospitalization. Further comparison was also made among those who developed treatment failure and who did not and among the survivors and deaths. RESULTS: SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%; p<0.001) and fatal outcome (21% vs. 4%; p<0.001) compared to those without danger signs. Only 6/111 (5.4%) SAM children with danger signs of severe pneumonia and 12/296 (4.0%) without danger signs had bacterial isolates from blood. In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia, and bacteraemia were independently associated both with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p<0.01). CONCLUSION AND SIGNIFICANCE: The result suggests that SAM children with cough or respiratory difficulty and radiologic pneumonia who had WHO-defined danger signs of severe pneumonia more often had treatment failure and fatal outcome compared to those without the danger signs. In addition to danger signs of severe pneumonia, other common causes of both treatment failure and deaths were dehydration, hypocalcaemia, and bacteraemia on admission. The result underscores the importance for further research especially a randomized, controlled clinical trial to validate standard WHO therapy in SAM children with pneumonia especially with danger signs of severe pneumonia to reduce treatment failures and deaths.

Severe Sepsis in Severely Malnourished Young Bangladeshi Children with Pneumonia: A Retrospective Case Control Study.

BACKGROUND: In developing countries, there is no published report on predicting factors of severe sepsis in severely acute malnourished (SAM) children having pneumonia and impact of fluid resuscitation in such children. Thus, we aimed to identify predicting factors for severe sepsis and assess the outcome of fluid resuscitation of such children. METHODS: In this retrospective case-control study SAM children aged 0-59 months, admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh from April 2011 through July 2012 with history of cough or difficult breathing and radiologic pneumonia, who were assessed for severe sepsis at admission constituted the study population. We compared the pneumonic SAM children with severe sepsis (cases = 50) with those without severe sepsis (controls = 354). Severe sepsis was defined with objective clinical criteria and managed with fluid resuscitation, in addition to antibiotic and other supportive therapy, following the standard hospital guideline, which is very similar to the WHO guideline. RESULTS: The case-fatality-rate was significantly higher among the cases than the controls (40% vs. 4%; p<0.001). In logistic regression analysis after adjusting for potential confounders, lack of BCG vaccination, drowsiness, abdominal distension, acute kidney injury, and metabolic acidosis at admission remained as independent predicting factors for severe sepsis in pneumonic SAM children (p<0.05 for all comparisons). CONCLUSION AND SIGNIFICANCE: We noted a much higher case fatality among under-five SAM children with pneumonia and severe sepsis who required fluid resuscitation in addition to standard antibiotic and other supportive therapy compared to those without severe sepsis. Independent risk factors and outcome of the management of severe sepsis in our study children highlight the importance for defining optimal fluid resuscitation therapy aiming at reducing the case fatality in such children.

Bubble continuous positive airway pressure for children with severe pneumonia and hypoxaemia in Bangladesh: an open, randomised controlled trial.

BACKGROUND: In developing countries, mortality in children with very severe pneumonia is high, even with the provision of appropriate antibiotics, standard oxygen therapy, and other supportive care. We assessed whether oxygen therapy delivered by bubble continuous positive airway pressure (CPAP) improved outcomes compared with standard low-flow and high-flow oxygen therapies. METHODS: This open, randomised, controlled trial took place in Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh. We randomly assigned children younger than 5 years with severe pneumonia and hypoxaemia to receive oxygen therapy by either bubble CPAP (5 L/min starting at a CPAP level of 5 cm H2O), standard low-flow nasal cannula (2 L/min), or high-flow nasal cannula (2 L/kg per min up to the maximum of 12 L/min). Randomisation was done with use of the permuted block methods (block size of 15 patients) and Fisher and Yates tables of random permutations. The primary outcome was treatment failure (ie, clinical failure, intubation and mechanical ventilation, death, or termination of hospital stay against medical advice) after more than 1 h of treatment. Primary and safety analyses were by intention to treat. We did two interim analyses and stopped the trial after the second interim analysis on Aug 3, 2013, as directed by the data safety and monitoring board. This trial is registered at ClinicalTrials.gov, number NCT01396759. FINDINGS: Between Aug 4, 2011, and July 17, 2013, 225 eligible children were recruited. We randomly allocated 79 (35%) children to receive oxygen therapy by bubble CPAP, 67 (30%) to low-flow oxygen therapy, and 79 (35%) to high-flow oxygen therapy. Treatment failed for 31 (14%) children, of whom five (6%) had received bubble CPAP, 16 (24%) had received low-flow oxygen therapy, and ten (13%) had received high-flow oxygen therapy. Significantly fewer children in the bubble CPAP group had treatment failure than in the low-flow oxygen therapy group (relative risk [RR] 0·27, 99·7% CI 0·07-0·99; p=0·0026). No difference in treatment failure was noted between patients in the bubble CPAP and those in the high-flow oxygen therapy group (RR 0·50, 99·7% 0·11-2·29; p=0·175). 23 (10%) children died. Three (4%) children died in the bubble CPAP group, ten (15%) children died in the low-flow oxygen therapy group, and ten (13%) children died in the high-flow oxygen therapy group. Children who received oxygen by bubble CPAP had significantly lower rates of death than the children who received oxygen by low-flow oxygen therapy (RR 0·25, 95% CI 0·07-0·89; p=0·022). INTERPRETATION: Oxygen therapy delivered by bubble CPAP improved outcomes in Bangladeshi children with very severe pneumonia and hypoxaemia compared with standard low-flow oxygen therapy. Use of bubble CPAP oxygen therapy could have a large effect in hospitals in developing countries where the only respiratory support for severe childhood pneumonia and hypoxaemia is low-flow oxygen therapy. The trial was stopped early because of higher mortality in the low-flow oxygen group than in the bubble CPAP group, and we acknowledge that the early cessation of the trial reduces the certainty of the findings. Further research is needed to test the feasibility of scaling up bubble CPAP in district hospitals and to improve bubble CPAP delivery technology. FUNDING: International Centre for Diarrhoeal Disease Research, Bangladesh, and Centre for International Child Health, University of Melbourne.

Validity of antibodies in lymphocyte supernatant in diagnosing tuberculosis in severely malnourished children presenting with pneumonia.

BACKGROUND: The diagnosis of tuberculosis (TB) in young children can be challenging, especially in severely malnourished children. There is a critical need for improved diagnostics for children. Thus, we sought to evaluate the performance of a technique that measures antibodies in lymphocyte supernatant (ALS) for the diagnosis of TB in severely malnourished children presenting with suspected pneumonia. METHODS: Children less than 5 years with severe acute malnutrition and radiological features of pneumonia admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh, were enrolled consecutively following informed written consent. In addition to clinical and radiological assessment, samples taken for TB diagnosis included gastric lavage fluid and induced sputum for microbiological confirmation. ALS was measured from venous blood, and results were evaluated in children classified as "confirmed", "non-confirmed TB" or "not TB". RESULTS: Among 224 children who had ALS analysis, 12 (5.4%) children had microbiologically "confirmed TB", a further 41 (18%) had clinically diagnosed "non-confirmed TB" and the remaining 168 (75%) were considered not to have TB. ALS was positive in 89 (40%) and negative in 85 (39%) of children, with a large number (47 or 21%) reported as "borderline". These proportions were similar between the three diagnostic groups. The sensitivity and specificity of ALS when comparing "Confirmed TB" to "Not TB" was only 67% (95% CI: 31-91%) and 51% (95% CI: 42-60%), respectively. CONCLUSIONS AND SIGNIFICANCE: Our data suggest that ALS is not sufficiently accurate to improve the diagnosis of TB in children with severe malnutrition.

Sociodemographic, Epidemiological, and Clinical Risk Factors for Childhood Pulmonary Tuberculosis in Severely Malnourished Children Presenting With Pneumonia: Observation in an Urban Hospital in Bangladesh.

We aimed to evaluate sociodemographic, epidemiological, and clinical risk factors for pulmonary tuberculosis (PTB) in children presenting with severe acute malnutrition (SAM) and pneumonia. Children aged 0 to 59 months with SAM and radiologic pneumonia from April 2011 to July 2012 were studied in Bangladesh. Children with confirmed PTB (by culture and/or X-pert MTB/RIF) (cases = 27) and without PTB (controls = 81; randomly selected from 378 children) were compared. The cases more often had the history of contact with active PTB patient (P < .01) and exposure to cigarette smoke (P = .04) compared with the controls. In logistic regression analysis, after adjusting for potential confounders, the cases were independently associated with working mother (P = .05) and positive tuberculin skin test (TST; P = .02). Thus, pneumonia in SAM children is a common presentation of PTB and further highlights the importance of the use of simple TST and/or history of contact with active TB patients in diagnosing PTB in such children, especially in resource-limited settings.

Post-discharge mortality in children with severe malnutrition and pneumonia in Bangladesh.

BACKGROUND: Post-discharge mortality among children with severe illness in resource-limited settings is under-recognized and there are limited data. We evaluated post-discharge mortality in a recently reported cohort of children with severe malnutrition and pneumonia, and identified characteristics associated with an increased risk of death. METHODS: Young children (<5 years of age) with severe malnutrition (WHO criteria) and radiographic pneumonia on admission to Dhaka Hospital of icddr,b over a 15-month period were managed according to standard protocols. Those discharged were followed-up and survival status at 12 weeks post-discharge was determined. Verbal autopsy was requested from families of those that died. RESULTS: Of 405 children hospitalized with severe malnutrition and pneumonia, 369 (median age, 10 months) were discharged alive with a follow-up plan. Of these, 32 (8.7%) died in the community within 3 months of discharge: median 22 (IQR 9-35) days from discharge to death. Most deaths were reportedly associated with acute onset of new respiratory or gastrointestinal symptoms. Those that died following discharge were significantly younger (median 6 [IQR 3,12] months) and more severely malnourished, on admission and on discharge, than those that survived. Bivariate analysis found that severe wasting on admission (OR 3.64, 95% CI 1.66-7.97) and age <12 months (OR 2.54, 95% CI 1.1-8.8) were significantly associated with post-discharge death. Of those that died in the community, none had attended a scheduled follow-up and care-seeking from a traditional healer was more common (p<0.001) compared to those who survived. CONCLUSION AND SIGNIFICANCE: Post-discharge mortality was common in Bangladeshi children following inpatient care for severe malnutrition and pneumonia. The underlying contributing factors require a better understanding to inform the potential of interventions that could improve survival.