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.

Anti-rotavirus protein reduces stool output in infants with diarrhea: a randomized placebo-controlled trial.

BACKGROUND & AIMS: Rotavirus infection is a leading cause of morbidity and mortality in children younger than 5 years of age. Current treatment options are limited. We assessed the efficacy of a llama-derived, heavy-chain antibody fragment called anti-rotavirus protein (ARP1), in modifying the severity and duration of diarrhea in male infants with rotavirus infection. METHODS: We performed a double-blind, placebo-controlled trial of 176 male infants (6-24 months old) with severe rotavirus-associated diarrhea at Dhaka Hospital, Bangladesh. The infants were randomly assigned to groups given oral ARP1 (15-30 mg/kg/day, n = 88) or placebo (maltodextrin, n = 88) for a maximum of 5 days. The primary outcomes were severity (stool output) and duration of diarrhea and fecal excretion of rotavirus. Secondary outcomes were intake of oral rehydration salt solution, severity of vomiting, and serum levels of rotavirus-specific IgA. RESULTS: In infants with only rotavirus infection, total cumulative stool output was 305.47 g/kg body weight among those given placebo (n = 63) and 237.03 g/kg body weight among those given ARP1 (n = 61) (a difference of 68.44 g/kg body weight or 22.5%; 95% confidence interval: 18.27-118.59 g/kg body weight; P =.0079). There was a significant reduction in rate of stool output (g/kg/d) in the ARP1 group compared with the placebo group (61%; P = .002). ARP1 had no significant effect in infants with concomitant infections or on any other measured outcomes. No adverse events could be linked to ARP1. CONCLUSIONS: In a placebo-controlled trial, ARP1 reduced stool output in male infants with severe rotavirus-associated diarrhea. Clinicaltrials.gov number: NCT01259765.

Observational follow-up study on a cohort of children with severe pneumonia after discharge from a day-care clinic in Dhaka, Bangladesh.

Compliance, morbidity, mortality, and hospitalization during fortnightly follow-up were evaluated by an observational study on a cohort of children with severe and very severe pneumonia after day-care treatment at an urban clinic. The primary outcome measures were proportions of success (compliance) and failure (non-compliance) of follow-up visits at the day-care clinic. In total, 251 children were followed up, with median (IQR) age of 5.0 (3.0-9.0) months, and their compliance dropped from 92% at the first to 85% at the sixth visit. Cough (28%), fever (20%), and rapid breathing (13%) were common morbidities. Successful follow-up visits were possible in 180 (95.2%) and 56 (90.3%) of the children with severe and very severe pneumonia respectively. Eleven (4.4%) needed hospitalization, and four (1.6%) died. Majority (approximately 90%) of the children could be successfully followed up; some failed to attend their scheduled follow-up visits due to hospitalization and death. The common morbidities indicate the importance of follow-up for detecting medical problems and early treatment, thus reducing risk of death.

Prevalence, clinical predictors, and outcome of hypocalcaemia in severely-malnourished under-five children admitted to an urban hospital in Bangladesh: a case-control study.

Hypocalcaemia is common in severely-malnourished children and is often associated with fatal outcome. There is very limited information on the clinical predicting factors of hypocalcaemia in hospitalized severely-malnourished under-five children. Our objective was to evaluate the prevalence, clinical predicting factors, and outcome of hypocalcaemia in such children. In this case-control study, all severely-malnourished under-five children (n=333) admitted to the Longer Stay Ward (LSW), High Dependency Unit (HDU), and Intensive Care Unit (ICU) of the Dhaka Hospital of icddr,b between April 2011 and April 2012, who also had their total serum calcium estimated, were enrolled. Those who presented with hypocalcaemia (serum calcium <2.12 mmol/L) constituted the cases (n=87), and those admitted without hypocalcaemia (n=246) constituted the control group in our analysis. The prevalence of hypocalcaemia among severely-malnourished under-five children was 26% (87/333). The fatality rate among cases was significantly higher than that in the controls (17% vs 5%; p < 0.001). Using logistic regression analysis, after adjusting for potential confounders, such as vomiting, abdominal distension, and diastolic hypotension, we identified acute watery diarrhoea (AWD) (OR 2.19, 95% CI 1.08-4.43, p = 0.030), convulsion on admission (OR 21.86, 95% CI 2.57-185.86, p = 0.005), and lethargy (OR 2.70, 95% CI 1.633-5.46, p = 0.006) as independent predictors of hypocalcaemia in severely-malnourished children. It is concluded, severely-malnourished children presenting with hypocalcaemia have an increased risk of death than those without hypocalcaemia. AWD, convulsion, and lethargy assessed on admission to hospital are the clinical predictors of hypocalcaemia in such children. Presence of these features in hospitalized children with severe acute malnutrition (SAM) should alert clinicians about the possibility of hypocalcaemia and may help undertake potential preventive measures, such as calcium supplementation, in addition to other aspects of management of such children, especially in the resource-poor settings.

Clinical predictors and outcome of hypoxaemia among under-five diarrhoeal children with or without pneumonia in an urban hospital, Dhaka, Bangladesh.

OBJECTIVE: To explore the predictors and outcome of hypoxaemia in children under 5 years of age who were hospitalized for the management of diarrhoea in Dhaka, where comorbidities are common. METHODS: In a prospective cohort study, we enrolled all children <5 years of age admitted to the special care ward (SCW) of the Dhaka Hospital of ICDDR,B from September to December 2007. Those who presented with hypoxaemia (SpO(2) < 90%) constituted the study group, and those without hypoxaemia formed the comparison group. RESULTS: A total of 258 children were enrolled, all had diarrhoea. Of the total, 198 (77%) had pneumonia and 106 (41%) had severe malnutrition (<-3 Z-score of weight for age of the median of the National Centre for Health Statistics), 119 (46%) had hypoxaemia and 138 children did not have hypoxaemia at the time of admission. Children with hypoxaemia had a higher probability of a fatal outcome (21%vs. 4%; P < 0.001). Using logistic regression analysis, the independent predictors of hypoxaemia at the time of presentation were lower chest wall indrawing [OR 6.91, 95% confidence intervals (CI) 3.66-13.08, P < 0.001], nasal flaring (OR 3.22, 95% CI 1.45-7.17, P = 0.004) and severe sepsis (OR 4.48, 95% CI 1.62-12.42, P = 0.004). CONCLUSION: In this seriously ill population of children with diarrhoea and comorbidities, hypoxaemia was associated with high case-fatality rates. Independent clinical predictors of hypoxaemia in this population, identifiable at the time of admission, were lower chest wall indrawing, nasal flaring and the clinical syndrome of severe sepsis.

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.

Salovum egg yolk containing antisecretory factor as an adjunct therapy in severe cholera in adult males: a pilot study.

Cholera involves stimulation of intestinal secretory process in response to cholera toxin leading to profuse watery diarrhoea that might cause death due to dehydration unless timely rehydration therapy is initiated. Efforts to identify and test potential antisecretory agents are ongoing. Antisecretory factor (AF) is a naturally-occurring protein produced in the human secretory organs, including the intestine, with antisectory properties demonstrated in animal and human models of secretory diarrhoea. Salovum egg yolk powder contains antisecretory proteins in a much higher (500 times) concentration than that of normal hen eggs. This is achieved by feeding hens with specially-processed cereals, capable of inducing antisecretory proteins in the yolk. The aim of the study was to examine the effect of Salovum egg yolk powder containing AF in the treatment of adult cholera patients. In an open, randomized controlled trial (pilot study), 40 adult male patients with severe cholera were studied: 20 received standard treatment (oral rehydration solution, antibiotic, and usual hospital diet) plus Salovum egg yolk powder (study group) and 20 received standard treatment alone (control group). All the patients received tablet doxycycline (300 mg) once immediately after randomization. Written informed consent was obtained from each subject before enrollment. The main outcome measures were stool weight and duration of diarrhoea. The demographic and baseline clinical characteristics of the study patients were comparable between the groups. No significant differences were found in the mean stool weight, g/kg of body-weight during the first 24 hours [study vs control group, mean +/- standard deviation (SD), 218 +/- 119 vs 195 +/- 136], second 24 hours (mean +/- SD, 23 +/- 39 vs 22 +/- 34), and cumulative up to 72 hours (mean +/- SD, 245 +/- 152 vs 218 +/- 169). The duration (hours) of diarrhoea after admission in the hospital was also similar in both the groups (mean +/- SD, 33 +/- 14 vs 32 +/- 10). No adverse effect was observed. Salovum egg powder containing AF as an adjunct therapy in the treatment of severe cholera could not demonstrate any beneficial effect. Further studies with higher doses of Salovum egg yolk powder might be considered in future to establish its antisecretory effect.

Transferable quinolone resistance in Vibrio cholerae.

Ciprofloxacin was introduced for treatment of patients with cholera in Bangladesh because of resistance to other agents, but its utility has been compromised by the decreasing ciprofloxacin susceptibility of Vibrio cholerae over time. We correlated levels of susceptibility and temporal patterns with the occurrence of mutation in gyrA, which encodes a subunit of DNA gyrase, followed by mutation in parC, which encodes a subunit of DNA topoisomerase IV. We found that ciprofloxacin activity was more recently further compromised in strains containing qnrVC3, which encodes a pentapeptide repeat protein of the Qnr subfamily, members of which protect topoisomerases from quinolone action. We show that qnrVC3 confers transferable low-level quinolone resistance and is present within a member of the SXT integrating conjugative element family found commonly on the chromosomes of multidrug-resistant strains of V. cholerae and on the chromosomes of Escherichia coli transconjugants constructed in the laboratory. Thus, progressive increases in quinolone resistance in V. cholerae are linked to cumulative mutations in quinolone targets and most recently to a qnr gene on a mobile multidrug resistance element, resulting in further challenges for the antimicrobial therapy of cholera.

Evaluation of simple laboratory investigations to predict fatal outcome in infants with severe malnutrition presenting in an urban diarrhoea treatment centre in Bangladesh.

OBJECTIVE: To evaluate rapid and simple laboratory investigations to predict fatal outcome in infants presenting with diarrhoea and severe malnutrition. METHOD: Retrospective chart analysis of infants with severe malnutrition and diarrhoea with (cases) and without fatal outcome (controls) admitted to the Special Care Ward in Dhaka Hospital at ICDDR,B between May 2005 and April 2006. All infants (n=61) who underwent bedside blood glucose, full peripheral blood count, serum C-reactive protein (CRP), and serum electrolyte tests were included. RESULTS: In logistic regression analyses, after adjusting for all available potential confounders (abnormal WBC count, higher CRP level, hyponatraemia, hypokalaemia, hypocalcaemia, and hypomagnesaemia), cases (n=10) were significantly associated only with hypoglycaemia (measured using a portable bedside finger blood glucose test) (odds ratio 5.0, CI 1.1-23.0, P=0.039) on admission. CONCLUSION: A simple rapid bedside glucose test may be used to predict the outcome of diarrhoeal infants presenting with severe malnutrition.

Prevalence and risk factors of hepatitis B and C virus infections in an impoverished urban community in Dhaka, Bangladesh.

BACKGROUND: Viral hepatitis is a serious global public health problem affecting billions of people globally, and both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are rapidly spreading in the developing countries including Bangladesh due to the lack of health education, poverty, illiteracy and lack of hepatitis B vaccination. Also there is lack of information on their prevalence among the general population. So, a population-based serological survey was conducted in Dhaka to determine the prevalence and risk factors of HBV and HCV infections. METHODS: Healthy individuals were selected for demographic and behavioural characteristics by stratified cluster sampling and blood tested for hepatitis B surface antigen (HBsAg), antibody to HBV core antigen (anti-HBc), and anti-HCV antibodies (anti-HCV). RESULTS: From June 2005-November 2006, 1997 participants were screened for HBsAg, anti-HBc and anti-HCV, 738 (37%) were males with mean (SD) age of 24 (14) years. HBV-seropositivity was documented in 582 (29%) participants: 14 (0.7%) were positive for HBsAg, 452 (22.6%) for anti-HBc and 116 (5.8%) for both HBsAg and anti-HBc. Four (0.2%) participants were positive for anti-HCV, and another five (0.3%) for both anti-HBc and anti-HCV. Ninety-six/246 (39%) family members residing at same households with HBsAg positive participants were also HBV-seropositive [74 (30.1%) for anti-HBc and 22 (8.9%) for both HBsAg and anti-HBc], which was significantly higher among family members (39%) than that of study participants (29%) (OR 1.56; p < 0.001). In bivariate analysis, HBV-seropositivity was significantly associated with married status (OR 2.27; p < 0.001), history of jaundice (OR 1.35; p = 0.009), surgical operations (OR 1.26; p = 0.04), needle-stick injuries (OR 2.09; p = 0.002), visiting unregistered health-care providers (OR 1.40; p = 0.008), receiving treatment for sexually transmitted diseases (STD) (OR 1.79; p = 0.001), animal bites (OR 1.73; p < 0.001); ear-nose-body piercing in females (OR 4.97; p < 0.001); circumcision (OR 3.21; p < 0.001), and visiting community barber for shaving in males (OR 3.77; p < 0.001). In logistic regression analysis, married status (OR 1.32; p = 0.04), surgical operations (OR 1.39; p = 0.02), animal bites (OR 1.43; p = 0.02), visiting unregistered health-care providers (OR 1.40; p = 0.01); and ear-nose-body piercing in females (OR 4.97; p < 0.001) were significantly associated with HBV-seropositivity. CONCLUSIONS: The results indicate intermediate level of endemicity of HBV infection in Dhaka community, with much higher prevalence among family members of HBsAg positive individuals but low prevalence of HCV infections, clearly indicating need for universal hepatitis B vaccination. The use of disposable needles for ear-nose-body piercing need to be promoted through public awareness programmes as a preventive strategy.

Predictors of bacteremia in infants with diarrhea and systemic inflammatory response syndrome attending an urban diarrheal treatment center in a developing country.

OBJECTIVES: To identify clinical and laboratory predictors of bacteremia in infants with diarrhea and systemic inflammatory response syndrome and to analyze their outcome. STUDY DESIGN: Retrospective, case-control study. SETTING: The Special Care Ward of the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh, Dhaka, Bangladesh. PATIENTS: All the infants (n = 90) admitted to the Special Care Ward between May 2005 and April 2006 who had a blood culture, full peripheral blood count, and serum C-reactive protein performed were included in the study. Infant with systemic inflammatory response syndrome with confirmed bacteremia (n = 18) constituted cases, and those with systemic inflammatory response syndrome but negative blood culture (n = 72) constituted the controls. RESULTS: The following features were analyzed by comparing the two groups: absent or uncountable peripheral pulses, hypothermia, sclerema, altered mental status, white blood cell count, serum C-reactive protein, total protein concentrations, and outcome. The case-fatality rate was significantly higher among bacteremic infants compared with those without bacteremia (33% vs. 6%, p < .01). In the univariate model, sclerema (56% vs. 28%, p = .05), hyperglycemia (28% vs. 6%, p < .01), immature neutrophils [3.5 (00, 6.5) vs. 0.0 (0.0, 3.25); p = .02], higher C-reactive protein [2.7 (1.2, 7.4) vs. 1.8 (0.5, 4.2); p = .02], and lower serum total protein (51.1 +/- 14.1 vs. 57.6 +/- 12.2; p = .05) were identified as potential predictors of bacteremia. However, in the logistic regression analysis, after adjusting for confounders, only hypothermia (odds ratio = 6.4, 95% confidence Interval, 1.6-25.9; p = .01) and absent or uncountable peripheral pulse (odds ratio, 12.4, 95% confidence interval, 1.9-83.4; p < .01) remained significant independent predictors of bacteremia. CONCLUSIONS: Our data suggest that, in infants presenting with diarrhea and systemic inflammatory response syndrome, coexistence of hypothermia and absent or uncountable peripheral pulse is strongly associated with bacteremia. Bacteremia in this patient group is associated with high case-fatality rates.

Single-dose azithromycin for the treatment of cholera in adults.

BACKGROUND: Single-dose azithromycin is effective in the treatment of severe cholera in children, but its effectiveness in adults has not been evaluated. METHODS: We conducted a double-blind, randomized trial comparing the equivalence of azithromycin and ciprofloxacin (each given in a single 1-g dose of two 500-mg tablets) among 195 men with severe cholera caused by Vibrio cholerae O1 or O139. Patients were hospitalized for five days. A stool culture was performed daily. Primary outcome measures were clinical success (the cessation of watery stools within 48 hours after drug administration) and bacteriologic success (the inability to isolate V. cholerae after 48 hours). RESULTS: Therapy was clinically successful in 71 of 97 patients receiving azithromycin (73 percent) and in 26 of 98 patients receiving ciprofloxacin (27 percent) (P<0.001) and bacteriologically successful in 76 of 97 patients receiving azithromycin (78 percent) and in 10 of 98 patients receiving ciprofloxacin (10 percent) (P<0.001). Patients who were treated with azithromycin had a shorter duration of diarrhea than did patients treated with ciprofloxacin (median, 30 vs. 78 hours); a lower frequency of vomiting (43 percent vs. 67 percent); fewer stools (median, 36 vs. 52); and a lower stool volume (median, 114 vs. 322 ml per kilogram of body weight). The median minimal inhibitory concentration of ciprofloxacin for the 177 isolates of V. cholerae O1 was 0.25 mug per milliliter, which was 11 to 83 times as high as that in previous studies at this site. CONCLUSIONS: Single-dose azithromycin was effective in the treatment of severe cholera in adults. The lack of efficacy of ciprofloxacin may result from its diminished activity against V. cholerae O1 strains currently circulating in Bangladesh. (ClinicalTrials.gov number, NCT00229944.).

Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children.

BACKGROUND & AIMS: We investigated Helicobacter pylori (H pylori)-infection as a cause of iron deficiency (ID) and iron-deficiency anemia (IDA) or treatment failure of iron supplementation. METHODS: We randomized 200 Hp-infected children (positive urea breath test) 2-5 years of age with IDA (hemoglobin level <110 g/L; serum ferritin level <12 microg/L; and soluble transferrin receptor >8.3 mg/L) or ID (serum ferritin level <12 microg/L or soluble transferrin receptor level >8.3 mg/L) to 1 of 4 regimens: 2-week anti-Hp therapy (amoxicillin, clarithromycin, and omeprazole) plus 90-day oral ferrous sulfate (anti-Hp plus iron), 2-week anti-Hp therapy alone, 90-day oral iron alone, or placebo. Sixty noninfected children with IDA received iron treatment as negative control. RESULTS: Hp-infected children receiving iron had significantly less frequent treatment failure compared with those with no iron in correcting IDA (11% [95% confidence interval (CI), 2%-20%] for anti-Hp plus iron, 0% for iron alone vs 33% [95% CI, 26%-46%] for anti-Hp and 45% [95% CI, 31%-59%] for placebo; chi(2) = 127; P < .0001), ID (19% [95% CI, 8%-30%] for anti-Hp plus iron, 7% [95% CI, 0%-14%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone, and 78% [95% CI, 66%-90%] for placebo; chi(2) = 124; P < .0001), or anemia (34% [95% CI, 20%-40%] for anti-Hp plus iron, 27% [95% CI, 14%-40%] for iron alone vs 65% [95% CI, 52%-78%] for anti-Hp alone and 78% [95% CI, 66%-90%] for placebo; chi(2) = 46; P < .0001). Cure rates of IDA, ID, or anemia with iron were comparable with that of the negative control group. Improvements in iron status also were significantly greater in groups with iron. CONCLUSIONS: H pylori is neither a cause of IDA/ID nor a reason for treatment failure of iron supplementation in young Bangladeshi children.

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.

Single-dose ciprofloxacin versus 12-dose erythromycin for childhood cholera: a randomised controlled trial.

BACKGROUND: Single-dose ciprofloxacin is effective for the treatment of severe cholera in adults. We assessed whether single-dose ciprofloxacin would be as effective as 3-day, 12-dose erythromycin in achieving clinical cure in children with severe cholera. METHODS: We did a randomised, open label, controlled trial in children age 2-15 years with V cholerae O1 or O139 present in stool on dark-field microscopy. Children received either a single 20 mg/kg dose of ciprofloxacin (n=90) or 12.5 mg/kg of erythromycin (n=90) every 6 h for 3 days, and remained in hospital for 5 days. The primary outcome was clinical success of treatment, defined as cessation of watery stools within 48 h of start of drug treatment. Analysis was per protocol. This study is registered with the ClinicalTrials.gov Protocol Registration System at http://www.clinicaltrials.gov (registration number NCT 00142272) [corrected] FINDINGS: Of 180 children randomised 162 completed the study. Treatment was clinically successful in 60% (47/78) of children treated with ciprofloxacin and in 55% (46/84) of those treated with erythromycin (difference 5% [95% CI -10 to 21]). Children receiving ciprofloxacin vomited less often (58%vs 74%; difference 16% [2 to 30]), had fewer stools (15 vs 21; 6 [0 to 9]), and less stool volume (152 vs 196 mL/kg; 43 mL/kg [13 to 87]) than those receiving erythromycin. Bacteriological failure was more common in ciprofloxacin-treated patients (58%vs 30%; 28% [13 to 43]) than erythromycin-treated patients. INTERPRETATION: Single-dose ciprofloxacin achieves clinical outcomes similar to, or better than, those achieved with 12-dose erythromycin treatment in childhood cholera, but is less effective in eradicating V cholerae from stool.

Symptomatic hyponatremia during treatment of dehydrating diarrheal disease with reduced osmolarity oral rehydration solution.

CONTEXT: In May 2002, the World Health Organization and the United Nations Children's Fund recommended that the formulation of oral rehydration solution (ORS) for treatment of patients with diarrhea be changed to one with a reduced osmolarity and that safety of the new formulation, particularly development of symptomatic hyponatremia, be monitored. OBJECTIVE: To measure the rates of symptomatic hyponatremia during treatment of patients with diarrhea with reduced osmolarity ORS. DESIGN, SETTINGS, AND PATIENTS: A phase 4 trial conducted at the Dhaka hospital (December 1, 2002-November 30, 2003) and Matlab hospital (February 2, 2003-January 31, 2004) of the International Centre for Diarrhoeal Disease Research Bangladesh: Centre for Health and Population Research, Dhaka, Bangladesh. All patients admitted with uncomplicated watery diarrhea were treated with the newly recommended ORS and monitored. Patients developing neurological symptoms (seizure or altered consciousness) were transferred to the special care ward for treatment and investigated to identify the cause of the symptoms. Patient records of the Dhaka hospital were reviewed during the previous year when the old ORS formulation was used. INTERVENTION: Reduced osmolarity ORS. MAIN OUTCOME MEASURE: Incidence rate of symptomatic hyponatremia in a 1-year period. RESULTS: A total of 53,280 patients, including 22,536 children younger than 60 months, were monitored at the Dhaka and Matlab hospitals. Twenty-four patients, none older than 36 months, developed seizures or altered consciousness associated with hyponatremia, with an overall incidence rate of 0.05% (95% confidence interval [CI], 0.03%-0.07%) at the Dhaka hospital and 0.03% (95% CI, 0.01%-0.09%) at the Matlab hospital. During the previous year, 47 patients at the Dhaka hospital had symptoms associated with hyponatremia, for an estimated incidence rate of 0.10% (95% CI, 0.07%-0.13%). The reduction in the rates was statistically significant (odds ratio, 0.50; 95% CI, 0.29-0.85; P = .009). CONCLUSION: The risk of symptoms associated with hyponatremia in patients treated with the reduced osmolarity ORS is minimal and did not increase with the change in formulation.

Analysis of fecal leukocytes and erythrocytes in Shigella infections in urban Bangladesh.

We evaluated the usefulness of enumeration of fecal leukocytes and erythrocytes in making an early diagnosis of Shigella infection, where Shigella is a leading cause of invasive diarrhea. Stool specimens from 561 invasive diarrhea patients were submitted for microscopic examination. A presumptive diagnosis of shigellosis based on microscopic examination was made in 389 of them; 227 had stool cultures positive for Shigella spp (Shigella patients). One hundred sixty-two patients with no detectable Shigella infection (non-Shigella invasive diarrhea cases) served as a comparison group. Two hundred twenty-seven randomly selected Shigella patients and 227 non-Shigella infectious diarrhea cases from the surveillance system database of the hospital constituted another group for comparative evaluation. The stool specimens of the patients were examined under the microscope, and isolation, biochemical characterization and serotyping of Shigella were performed. In comparison with non-Shigella invasive diarrhea cases, the presence of >50 WBC/hpf in association with any number of RBC in the fecal sample had a modest sensitivity of 67%, specificity of 59%, positive predictive value of 70%, negative predictive value of 56%, accuracy of 64%, and positive likelihood ratio of 1.6 in predicting shigellosis. Comparison between Shigella and non-Shigella infectious diarrhea patients revealed the presence of >20 WBC/hpf was a less accurate predictor of shigellosis (sensitivity 51%, specificity 88%, positive predictive value 81%, negative predictive value 64%, accuracy 69%, and positive likelihood ratio 4.1). Direct microscopical examination of stool specimens for the presence of WBC and RBC may facilitate the early diagnosis of shigellosis, and may be a cheap alternative to stool culture in this setting.

Childhood anemia and vitamin a deficiency in rural Bangladesh.

The study aimed to assess the prevalence of anemia and vitamin A deficiency in preschool children in rural Bangladesh. A cross-sectional study was done on eight randomly-selected sub-districts of rural Bangladesh. Children (n=1,302) aged 2-6 years were studied. Families of 43% of the study participants had a monthly household expenditure of US$ 60 or less. Fifty-six percent of the children were underweight, and 17% were severely underweight; 18% were wasted, and 1% were severely wasted; and 45% were stunted while 20% were severely stunted. The mean+/-SD serum retinol of the children was1.0+/-0.4 micromol/l, and 3% of them had serum retinol levels of <0.35 micromol/l, about one-fifth (20%) had a serum retinol level of <0.70 micromol/l and 55% had serum retinol levels of <1.05 pmol/l. The mean hemoglobin concentration of the children was 110+/-11 g/l, and 48% had a Hb of <11 g/l signifying anemia in this age group. Thirty-one percent (31 %) of children had low serum ferritin (<12 microg/l), and 14% had elevated CRP (> or = 15 mg/l) indicating the presence of a sub-clinical infection. Male and female children had similar nutritional status and biochemical profiles although boys tended to be heavier than girls (p=0.013). The proportion of children with anemia and iron deficiency anemia (IDA) declined significantly (p<0.001) with advancing age. Five percent of the study children had IDA and concomitant low serum retinol. The proportion of children with IDA and serum retinol also declined significantly with increasing age from 8% in children aged 35 months or younger, to 3% in children aged 60 months and more (p=0.025). Results of our study clearly demonstrated the public health importance of anemia and vitamin A deficiency among children of rural Bangladesh.