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.

Prevalence, clinical features, and outcome of pseudomonas bacteremia in under-five diarrheal children in bangladesh.

We sought to evaluate the prevalence, associated factors, and outcome of under-five diarrheal children with either sex having Pseudomonas bacteremia. A retrospective chart review of under-five diarrheal children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), from January 2011 to December 2011 was performed using an online hospital management system. Children with Pseudomonas bacteremia constituted the cases (n = 31), and the controls (n = 124), without Pseudomonas bacteremia, were randomly selected. The prevalence of Pseudomonas bacteremia was 1% (31/5,179). The Pseudomonas was multidrug resistant but was 84% sensitive to ceftazidime and 100% to imipenem. The case-fatality rate was significantly higher among the cases than the controls (26% versus 5%; P = 0.003). In logistic regression analysis, after adjusting for potential confounders such as severe wasting, severe underweight, severe pneumonia, and young age (11.71 (4.0, 18.0) months), the cases more often presented with absent peripheral pulses in absence of dehydration (95% CI = 2.31-24.45) on admission. This finding underscores the importance of early identification of this simple clinical sign to ensure prompt management including fluid resuscitation and broad spectrum antibiotics to help reduce morbidity and mortality in such children, especially in resource-poor settings.

Pulmonary tuberculosis in severely-malnourished or HIV-infected children with pneumonia: a review.

Presentation of pulmonary tuberculosis (PTB) as acute pneumonia in severely-malnourished and HIV-positive children has received very little attention, although this is very important in the management of pneumonia in children living in communities where TB is highly endemic. Our aim was to identify confirmed TB in children with acute pneumonia and HIV infection and/or severe acute malnutrition (SAM) (weight-for-length/height or weight-for-age z score <-3 of the WHO median, or presence of nutritional oedema). We conducted a literature search, using PubMed and Web of Science in April 2013 for the period from January 1974 through April 2013. We included only those studies that reported confirmed TB identified by acid fast bacilli (AFB) through smear microscopy, or by culture-positive specimens from children with acute pneumonia and SAM and/or HIV infection. The specimens were collected either from induced sputum (IS), or gastric lavage (GL), or broncho-alveolar lavage (BAL), or percutaneous lung aspirates (LA). Pneumonia was defined as the radiological evidence of lobar or patchy consolidation and/or clinical evidence of severe/ very severe pneumonia according to the WHO criteria of acute respiratory infection. A total of 17 studies met our search criteria but 6 were relevant for our review. Eleven studies were excluded as those did not assess the HIV status of the children or specify the nutritional status of the children with acute pneumonia and TB. We identified only 747 under-five children from the six relevant studies that determined a tubercular aetiology of acute pneumonia in children with SAM and/or positive HIV status. Three studies were reported from South Africa and one each from the Gambia, Ethiopia, and Thailand where 610, 90, 35, and 12 children were enrolled and 64 (10%), 23 (26%), 5 (14%), and 1 (8%) children were identified with active TB respectively, with a total of 93 (12%) children with active TB. Among 610 HIV-infected children in three studies from South Africa and 137 SAM children from other studies, 64 (10%) and 29 (21%) isolates of M. tuberculosis were identified respectively. Children from South Africa were infected with HIV without specification of their nutritional status whereas children from other countries had SAM but without indication of their HIV status. Our review of the existing data suggests that pulmonary tuberculosis may be more common than it is generally suspected in children with acute pneumonia and SAM, or HIV infection. Because of the scarcity of data, there is an urgent need to investigate PTB as one of the potential aetiologies of acute pneumonia in these children in a carefully-conducted larger study, especially outside Africa.

Interstitial lung disease and profound hypoxaemia in a severely-malnourished child with very severe pneumonia and potential lymph-node tuberculosis: an uncommon but serious co-morbidity.

A nine-month old boy was initially admitted at the Acute Respiratory Infection Unit of Dhaka Hospital of icddr,b and soon after transferred to the Intensive Care Unit of the same hospital. The boy had problems of very severe pneumonia (confirmed by radiology), severe hypoxaemia, severe malnutrition, and Down's syndrome. The patient was treated according to the hospital protocol for the management of pneumonia and malnutrition. During the hospital stay, hypoxaemia was persistent with very little improvement of pneumonia; a number of differentials, such as pneumocystis jirovecii pneumonia, lymph-node tuberculosis, were added to the problems. Subsequently, the patient's hypoxaemia improved with the empirical use of antitubercular drugs. However, the patient again developed persistent hypoxaemia and, after unsuccessful treatment for a hospital-acquired pneumonia, the problems further expanded to include interstitial lung disease (ILD). This was confirmed by high-resolution computed tomography, and the patient was treated with prednisolone for 6 months, along with antitubercular drugs. He fully recovered from ILD, hypoxaemia, and pneumonia both clinically and radiologically. Therefore, severely-malnourished children having wet cough and pneumonia with persistent hypoxaemia should be assessed for the possible existence of interstitial lung disease. This may help provide a prompt and appropriate management to reduce morbidity and deaths in such patients.

Recurrent sclerema in a young infant presenting with severe sepsis and severe pneumonia: an uncommon but extremely life-threatening condition.

A one month and twenty-five days old baby girl with problems of acute watery diarrhoea, severe dehydration, severe malnutrition, and reduced activity was admitted to the gastrointestinal unit of Dhaka Hospital of icddr,b. The differentials included dehydration, dyselectrolytaemia and severe sepsis. She was treated following the protocolized management guidelines of the hospital. However, within the next 24 hours, the patient deteriorated with additional problems of severe sepsis, severe pneumonia, hypoxaemia, ileus, and sclerema. She was transferred to the Intensive Care Unit (ICU). In the ICU, she was managed with oxygen supplementation, intravenous antibiotics, intravenous fluid, including a number of blood transfusions, vitamins, minerals, and diet. One month prior to this admission, she had been admitted to the ICU also with sclerema, septic shock, and urinary tract infection due to Escherichia coli and was discharged after full recovery. On both the occasions, she required repeated blood transfusions and aggressive antibiotic therapy in addition to appropriate fluid therapy and oxygen supplementation. She fully recovered from severe sepsis, severe malnutrition, ileus, sclerema, and pneumonia, both clinically and radiologically and was discharged two weeks after admission. Consecutive episodes of sclerema, resulting in two successive hospitalizations in a severely-malnourished young septic infant, have never been reported. However, this was managed successfully with blood transfusion, broad-spectrum antibiotics, and correction of electrolyte imbalance.

Use of only oral rehydration salt solution for successful management of a young infant with serum sodium of 201 mmol/L in an urban diarrhoeal diseases hospital, Bangladesh.

A boy aged 4 months 7 days was admitted to the Intensive Care Unit (ICU) of the Dhaka Hospital of icddr,b, Dhaka, Bangladesh, with the problems of acute watery diarrhoea with some dehydration, pneumonia, lethargy, and hypernatraemia (serum sodium of 201 mmol/L). Correction for hypernatraemia was tried by using only oral rehydration salt (ORS) solution. Seizures occurred during correction of the hypernatraemia. These were difficult to control and required three doses of injection lorazepam, a loading dose of injection phenobarbitone, followed by injection phenytoin and finally two doses of injection mannitol (even though there was no clinical or imaging evidence by ultrasonography or computed tomography of cerebral oedema). The correction was continued with ORS, and all the anticonvulsants were successfully weaned without any further seizures, and the patient recovered without any overt neurological sequelae. We present a case report of extreme hypernatraemia, which was successfully managed using only ORS.

Factors associated with encephalopathy in patients with Salmonella enterica serotype Typhi bacteremia presenting to a diarrheal hospital in Dhaka, Bangladesh.

To characterize clinical correlates of typhoid fever-associated encephalopathy, we performed a retrospective chart review of patients with Salmonella enterica serotype Typhi bacteremia who were hospitalized at the International Centre for Diarrhoeal Disease Research, Bangladesh, from February of 2009 to June of 2011. Of 207 patients bacteremic with Salmonella Typhi who were ≥ 5 years of age, we identified 43 (21%) patients with encephalopathy. Univariate analysis revealed that patients with encephalopathy more often presented at ages of 10-24 years and had severe dehydration, low oxygen saturation, high respiratory rate, low leukocyte count, low platelet count, and Widal flagellar H agglutinin (TH) titer ≥ 1:640 compared with typhoid patients without encephalopathy. Multivariate analysis using logistic regression showed that age, dehydration, leukocyte count, and Widal TH titer were independently associated with encephalopathy. Our findings suggest that age, severity of disease, and immune responses are associated with encephalopathy during Salmonella Typhi bacteremia, perhaps reflecting the impact of prominent inflammatory responses.

Ampicillin and gentamicin are a useful first-line combination for the management of sepsis in under-five children at an urban hospital in Bangladesh.

The study evaluated the commonly-used drugs for the management of sepsis and their outcome among under-five children. We evaluated the hospital-records of all paediatric sepsis patients (n = 183) in the intensive care unit (ICU) and longer-stay unit (LSU) of the Dhaka Hospital of icddr,b. These records were collected from the hospital management system (SHEBA) during November 2009 to October 2010. A total of 183 under-five children with clinical sepsis were found during the study period, and 14 (8%) of them were neonates. One hundred and eighty-one patients had received a combination of injection ampicilin and injection gentamicin, and two patients had received the combination of injection ceftriaxone and injection gentamicin. Only 46 (25%) patients required a change of antibiotics to the combination of intravenous ceftriaxone plus gentamicin after non-response of injection ampicilin and injection gentamicin combination; 7/181 (4%) patients died who received injection ampicilin and injection gentamicin whereas none died among the other two patients who received injection ceftriaxone and injection gentamicin (p = 1.00). The combination of injection ampicilin and injection gentamicin as the first-line antibiotics for the management of sepsis in children even beyond the neonatal age is very effective, resulting in lower mortality.

Impact of lack of breast feeding during neonatal age on the development of clinical signs of pneumonia and hypoxemia in young infants with diarrhea.

BACKGROUND: Hypoxemia is a grave sequel of pneumonia, and an important predictor of a fatal outcome. Pneumonia in the neonatal period is often associated with lack of breast feeding. However, there is no published report on the impact of the cessation of breast feeding in the neonatal period on the development of pneumonia and hypoxemia. The purpose of our study was to assess the impact of non-breast feeding or stopping breast feeding during the neonatal period (henceforth to be referred to as non-breast fed) on clinical features of pneumonia and hypoxemia in 0-6-month-old infants with diarrhea admitted to an urban hospital in Bangladesh. METHODS: We prospectively enrolled all infants (n = 107) aged 0 to 6 months who were admitted to the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research Bangladesh (ICDDR,B) with diarrhea and pneumonia from September 2007 through December 2007.We compared the clinical features of pneumonia and hypoxemia of breast fed infants (n = 34) with those who were non-breast fed (n = 73). RESULTS: The median (inter-quartile range) duration of hypoxemia (hours) in non-breast-feds was longer than breast-fed infants [0.0 (0.0, 12.0) vs. 12.0 (0.0, 21.75); p = 0.021]. After adjusting for potential confounders such as inability to drink, fever, head nodding, cyanosis, grunting respiration, and lower chest wall in drawing, the non-breast-fed infants with pneumonia along with diarrhea had a higher probability of cough (OR 9.09; CI 1.34-61.71; p = 0.024), hypoxemia (OR 3.32; CI 1.23-8.93; p = 0.017), and severe undernutrition (OR 3.42; CI 1.29-9.12; p = 0.014). CONCLUSIONS AND SIGNIFICANCE: Non-breast feeding or cessation of breast feeding during the neonatal period may substantially increase the incidence of severe malnutrition, incidence of cough, and both the incidence and duration of hypoxemia in young infants presenting with pneumonia and diarrhea. The findings emphasize the paramount importance of the continuation of breast feeding in the neonatal period and early infancy.

Extending prayer marks as a sign of worsening chronic disease.

A 60-year-old Muslim man was admitted to the Dhaka Hospital of ICDDR,B with an exacerbation of his chronic obstructive pulmonary disease. Incidental hyperpigmented skin lesions were noticed overlying the dorsum of his ankles, knees, and elbows. Such asymptomatic areas of thickened, lichenified and hyperpigmented skin are called 'prayer marks' and are well-imprinted on the knees, ankles, and forehead. These are secondary to prolonged periods of pressure over bony prominences during prayer. The patient's wife stated that the appearance of the elbow marks had coincided with an increase in his breathlessness and subsequent use of his elbows to rise from daily prayers. Prayer marks extending to the elbows could be a sign of worsening chronic disease.

Predictors of death in under-five children with diarrhoea admitted to a critical care ward in an urban hospital in Bangladesh.

AIM: To evaluate the clinical and laboratory predictors of death in hospitalized under-five children with diarrhoea. METHODS: This is a prospective cohort study carried out in the Special Care Ward (SCW) of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh. All admitted diarrhoeal children of both sexes, aged 0-59 months, from September 2007 through December 2007 were enrolled. We compared and analysed factors among diarrhoeal children who died (n = 29) with those who survived (n = 229). RESULTS: In logistic regression analysis, after adjusting for potential confounders (infusion of intravenous fluid and immature PMN), absent peripheral pulse even after complete rehydration (OR 10.9, 95% CI 2.1-56.8; p < 0.01), severe malnutrition (OR 7.9, 95% CI 1.8-34.8; p < 0.01), hypoxaemia (OR 8.5, 95% CI 1.0-75.0; p = 0.05), radiological lobar pneumonia (OR 17.8, 95% CI 3.7-84.5; p < 0.01) and hypernatraemia (OR 15.8, 95% CI 3.0-81.8; p < 0.01) were independently associated with deaths among diarrhoeal children admitted to SCW. CONCLUSIONS: Thus, the absence of peripheral pulses even after full rehydration, severe malnutrition, hypoxaemia, lobar pneumonia and hypernatraemia are independent predictors of death among the under-five children with diarrhoea admitted to critical care ward of a resource-limited setting in Bangladesh.

Salmonella Typhi and Plasmodium falciparum co-infection in a 12-year old girl with haemoglobin E trait from a non-malarious area in Bangladesh.

A 12-year old girl from Uttar Badda, Dhaka, Bangladesh, was admitted to the Dhaka Hospital of ICDDR,B, with a 23-day history of fever and diarrhoea. After admission, she was treated for culture-proven Salmonella Typhi-associated infection and was discovered to be heterozygous for haemoglobin E. Despite treatment with appropriate antibiotics, the patient's condition did not improve, prompting further investigation, which revealed malaria due to Plasmodium falciparum. Dhaka is considered a malaria-free zone, and the patient denied recent travel outside Dhaka. Subsequently, the patient recovered fully on antimalarial therapy.

Hereditary spherocytosis.

A 12-year-old girl was brought to the Dhaka Hospital of ICDDR,B with diarrhoea. Incidentally, the parents provided a history of repeated episodes of pallor and jaundice since she was two and half years old. Three of her family members had similar problems. History, clinical examination, and laboratory findings of the girl and her family members suggested a case of hereditary spherocytosis. To our knowledge, this is the first report of such a case in Bangladesh.

Typhus fever: an overlooked diagnosis.

A case of typhus fever is presented. On admission, the clinical diagnosis was typhoid fever. Forty-eight hours after admission, the presence of subconjunctival haemorrhage, malena, and jaundice raised the possibility of a different aetiology, the two most likely differentials being dengue and typhus. Finally, a co-infection of typhoid and typhus was discovered. This uncommon clinical scenario should be taken into account in the management of patients with high fever on admission being treated as a case of typhoid fever.

Occult pneumonia: an unusual but perilous entity presenting with severe malnutrition and dehydrating diarrhoea.

A three-month old boy was admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Dhaka, Bangladesh, with the problems of acute watery diarrhoea with some dehydration and suspected dyseletrolytaemia, severe malnutrition, and reduced activity. Occult pneumonia was added to the problem list after demonstration of radiologic consolidation in right upper lung, despite the lack of clinical signs, both on admission and after correction of dehydration. The problem list was further expanded to include bacteraemia due to Staphylococcus aureus when the blood culture report was available. Severely-malnourished children may not exhibit typical clinical signs of pneumonia, and the possibility of existence of such problems should be remembered in the assessment and provision of care to hospitalized young children with severe malnutrition.