Citrulline and kynurenine to tryptophan ratio: potential EED (environmental enteric dysfunction) biomarkers in acute watery diarrhea among children in Bangladesh.

Two emerging biomarkers of environmental enteric dysfunction (EED) include plasma citrulline (CIT), and the kynurenine (KYN): tryptophan (TRP)/ (KT) ratio. We sought to investigate the plasma concentration of CIT and KT ratio among the children having dehydrating diarrhea and examine associations between concentrations of CIT and KT ratio with concurrent factors. For this analysis, we used cross-sectional data from a total of 102, 6-36 months old male children who suffered from non-cholera acute watery diarrhea and had some dehydration admitted to an urban diarrheal hospital, in Bangladesh. CIT, TRP, and KYN concentrations were determined at enrollment from plasma samples using ELIZA. At enrollment, the mean plasma CIT concentration was 864.48 ± 388.55 µmol/L. The mean plasma kynurenine, tryptophan concentrations, and the KT ratio (× 1000) were 6.93 ± 3.08 µmol/L, 33.44 ± 16.39 µmol/L, and 12.12 ± 18.10, respectively. With increasing child age, KYN concentration decreased (coefficient: - 0.26; 95%CI: - 0.49, - 0.04; p = 0.021); with increasing lymphocyte count, CIT concentration decreased (coef.: - 0.01; 95% CI: - 0.02,0.001, p = 0.004); the wasted child had decreased KT ratio (coef.: - 0.6; 95% CI: - 1.18, - 0.02; p = 0.042) after adjusting for potential covariates. The CIT concentration was associated with blood neutrophils (coef.: 0.02; 95% CI: 0.01, 0.03; p < 0.001), lymphocytes (coef.: - 0.02; 95% CI: - 0.03, - 0.02; p < 0.001) and monocyte (coef.: 0.06; 95% CI: 0.01, 0.11; p = 0.021); KYN concentration was negatively associated with basophil (coef.: - 0.62; 95% CI: - 1.23, - 0.01; p = 0.048) after adjusting for age. In addition, total stool output (gm) increased (coef.: 793.84; 95% CI: 187.16, 1400.52; p = 0.011) and also increased duration of hospital stay (hour) (coef.: 22.89; 95% CI: 10.24, 35.54; p = 0.001) with increasing CIT concentration. The morphological changes associated with EED may increase the risk of enteric infection and diarrheal disease among children. Further research is critically needed to better understand the complex mechanisms by which EED biomarkers may impact susceptibility to dehydrating diarrhea in children.

A double-blind clinical trial to compare the efficacy and safety of a multiple amino acid-based ORS with the standard WHO-ORS in the management of non-cholera acute watery diarrhea in infants and young children: "VS002A" trial protocol.

BACKGROUND: Diarrhea is the second deadliest disease for under-five children globally and the situation is more serious in developing countries. Oral rehydration solution (ORS) is being used as a standard treatment for acute watery diarrhea for a long time. Our objective is to compare the efficacy of amino acid-based ORS "VS002A" compared to standard glucose-based WHO-ORS in infants and young children suffering from acute non-cholera watery diarrhea. METHODS: It is a randomized, double-blind, two-cell clinical trial at Dhaka Hospital of icddr,b. A total of 312 male children aged 6-36 months old with acute non-bloody watery diarrhea are included in this study. Intervention arm participants get amino acid-based ORS (VS002A) and the control arm gets standard glucose-based WHO-ORS. The primary efficacy endpoint is the duration of diarrhea in the hospital. DISCUSSION: Oral rehydration therapy (ORT) with the present ORS formulation has certain limitations - it does not reduce the volume, frequency, or duration of diarrhea. Additionally, the failure of present standard ORS to significantly reduce stool output likely contributes to the relatively limited use of ORS by mothers as they do not feel that ORS is helping their child recover from the episode of diarrhea. Certain neutral amino acids (e.g., glycine, L-alanine, L-glutamine) can enhance the absorption of sodium ions and water from the gut. By using this concept, a shelf-stable, sugar-free amino acid-based hydration medicinal food named 'VS002A' that effectively rehydrates, and improves the barrier function of the bowel following infections targeting the gastrointestinal tract has been developed. If the trial shows significant benefits of VS002A use, this may provide evidence to support consideration of the use of VS002A in the present WHO diarrhea management guidelines. Conversely, if there is no evidence of benefit, these results will reaffirm the current guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT04677296 . Registered on December 21, 2020.

Different Features of Cholera in Malnourished and Non-Malnourished Children: Analysis of 20 Years of Surveillance Data from a Large Diarrheal Disease Hospital in Urban Bangladesh.

Malnourished children are more prone to infectious diseases including severe diarrhea compared to non-malnourished children. However, data are scarce on differences in the presentation in such children. We aimed to identify clinical differentials among children with cholera with or without malnutrition. Data were extracted from the diarrheal disease surveillance system (DDSS) of Dhaka Hospital of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) from January 2001 to December 2020. Among children under five in DDSS, cholera positive (culture confirmed) malnourished children (WAZ, WL/HZ or L/HAZ ˂ -2) were considered as cases (n = 920) and children with cholera but non-malnourished (WAZ, WL/HZ or L/HAZ ≥-2.00 to ≤+2.00) were controls (n = 586). After adjusting for potential confounders such as maternal illiteracy, day labor fathers, maternal employment, slum dwelling, non-sanitary latrine use, use of untreated water, and history of cough, it was revealed that malnourished cholera children significantly more often presented in hospital during evening hours (6 p.m. to 12 mid-night) (p < 0.05), had illiterate fathers (p < 0.05), >24 h history of diarrheal duration (p < 0.05), dehydrating diarrhea (p < 0.05), and had longer hospitalization (p < 0.05). The study results underscore the importance of understanding of basic differences in the presentation of severity of cholera in malnourished children for prompt identification and subsequent management of these vulnerable children.

Risk Factors for Death in Bangladeshi Children Under 5 Years of Age Hospitalized for Diarrhea and Severe Respiratory Distress in an Urban Critical Care Ward.

Children with diarrhea hospitalized for respiratory distress often have fatal outcome in resource-limited settings, although data are lacking on risk factors for death in such children. We sought to evaluate clinical predictors for death in such children. In this prospective cohort study, we enrolled under-5 children with diarrhea admitted with severe respiratory distress to the intensive care unit of Dhaka Hospital of International Centre for Diarhoeal Disease Research, Bangladesh, from September 2014 through September 2015. We compared clinical and laboratory characteristics between study children those who died (n = 29) and those who survived (n = 62). In logistic regression analysis, after adjusting for potential confounders, the independent predictors for death in children hospitalized for diarrhea and severe respiratory distress were severe sepsis and hypoglycemia (P < .05 for all). Thus, recognition of these simple parameters may help clinicians identify children with diarrhea at risk of deaths in order to initiate prompt management for the better outcome, especially in resource-poor settings.

Ileus in children presenting with diarrhea and severe acute malnutrition: A chart review.

BACKGROUND: Severely malnourished children aged under five years requiring hospital admission for diarrheal illness frequently develop ileus during hospitalization with often fatal outcomes. However, there is no data on risk factors and outcome of ileus in such children. We intended to evaluate predictive factors for ileus during hospitalization and their outcomes. METHODOLOGY/PRINCIPAL FINDINGS: This was a retrospective chart review that enrolled severely malnourished children under five years old with diarrhea, admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh between April 2011 and August 2012. We used electronic database to have our chart abstraction from previously admitted children in the hospital. The clinical and laboratory characteristics of children with (cases = 45), and without ileus (controls = 261) were compared. Cases were first identified by observation of abnormal bowel sounds on physical examination and confirmed with abdominal radiographs. For this comparison, Chi-square test was used to measure the difference in proportion, Student's t-test to calculate the difference in mean for normally distributed data and Mann-Whitney test for data that were not normally distributed. Finally, in identifying independent risk factors for ileus, logistical regression analysis was performed. Ileus was defined if a child developed abdominal distension and had hyperactive or sluggish or absent bowel sound and a radiologic evidence of abdominal gas-fluid level during hospitalization. Logistic regression analysis adjusting for potential confounders revealed that the independent risk factors for admission for ileus were reluctance to feed (odds ratio [OR] = 3.22, 95% confidence interval [CI] = 1.24-8.39, p = 0.02), septic shock (OR = 3.62, 95% CI = 1.247-8.95, p<0.01), and hypokalemia (OR = 1.99, 95% CI = 1.03-3.86, p = 0.04). Mortality was significantly higher in cases compared to controls (22% vs. 8%, p<0.01) in univariate analysis; however, in multivariable regression analysis, after adjusting for potential confounders such as septic shock, no association was found between ileus and death (OR = 2.05, 95% CI = 0.68-6.14, p = 0.20). In a separate regression analysis model, after adjusting for potential confounders such as ileus, reluctance to feed, hypokalemia, hypocalcemia, and blood transfusion, septic shock (OR = 168.84, 95% CI = 19.27-1479.17, p<0.01) emerged as the only independent predictor of death in severely malnourished diarrheal children. CONCLUSIONS/SIGNIFICANCE: This study suggests that the identification of simple independent admission risk factors for ileus and risk factors for death in hospitalized severely malnourished diarrheal children may prompt clinicians to be more vigilant in managing these conditions, especially in resource-limited settings in order to decrease ileus and ileus-related fatal outcomes in such children.

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.

Oral application of Escherichia coli bacteriophage: safety tests in healthy and diarrheal children from Bangladesh.

A T4-like coliphage cocktail was given with different oral doses to healthy Bangladeshi children in a placebo-controlled randomized phase I safety trial. Fecal phage detection was oral dose dependent suggesting passive gut transit of coliphages through the gut. No adverse effects of phage application were seen clinically and by clinical chemistry. Similar results were obtained for a commercial phage preparation (Coliproteus from Microgen/Russia). By 16S rRNA gene sequencing, only a low degree of fecal microbiota conservation was seen in healthy children from Bangladesh who were sampled over a time interval of 7 days suggesting a substantial temporal fluctuation of the fecal microbiota composition. Microbiota variability was not associated with the age of the children or the presence of phage in the stool. Stool microbiota composition of Bangladeshi children resembled that found in children of other regions of the world. Marked variability in fecal microbiota composition was also seen in 71 pediatric diarrhea patients receiving only oral rehydration therapy and in 38 patients receiving coliphage preparations or placebo when sampled 1.2 or 4 days apart respectively. Temporal stability of the gut microbiota should be assessed in case-control studies involving children before associating fecal microbiota composition with health or disease phenotypes.

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.

Factors Associated with Streptococcal Bacteremia in Diarrheal Children under Five Years of Age and Their Outcome in an Urban Hospital in Bangladesh.

BACKGROUND: Although Streptococcal bacteremia is common in diarrheal children with high morbidity and mortality, no systematic data are available on Streptococcal bacteremia in diarrheal children. We sought to evaluate the factors associated with Streptococcal bacteremia in diarrheal children under five years of age and their outcome. METHODS: We used an unmatched case-control design to investigate the associated factors with Streptococcal bacteremia in all the diarrheal children under five years of age through electronic medical record system of Dhaka hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We had simultaneously used a retrospective cohort design to further evaluate the outcome of our study children. All the enrolled children had their blood culture done between January 2010 and December 2012. Comparison was made among the children with (cases = 26) and without Streptococcal bacteremia (controls = 78). Controls were selected randomly from hospitalized diarrheal children under five years of age. RESULTS: Cases had proportionately higher deaths compared to controls, but it was statistically insignificant (15% vs. 10%, p = 0.49). The cases more often presented with severe dehydration, fever, respiratory distress, severe sepsis, and abnormal mental status compared to the controls (for all p<0.05). In the logistic regression analysis, after adjusting for potential confounders, it has been found that Streptococcal bacteremia in diarrheal children under five years of age was independently associated with nutritional edema (OR: 5.86, 95% CI = 1.28-26.80), hypoxemia (OR: 19.39, 95% CI = 2.14-175.91), fever (OR: 4.44, 95% CI = 1.13-17.42), delayed capillary refill time (OR: 7.00, 95% CI = 1.36-35.93), and respiratory distress (OR: 2.69, 95% CI = 1.02-7.12). CONCLUSIONS AND SIGNIFICANCE: The results of our analyses suggest that diarrheal children under five years of age presenting with nutritional edema, hypoxemia, fever, delayed capillary refill time, and respiratory distress may be at risk of Streptococcal bacteremia. It underscores the importance of identification of these simple clinical parameters for the prompt recognition and management in order to reduce the morbidity and death of such children especially in resource limited settings.

Hypernatremia in Children With Diarrhea: Presenting Features, Management, Outcome, and Risk Factors for Death.

We sought to investigate the magnitude, clinical features, treatment, and outcome of children suffering from hypernatremic diarrhea and to identify risk factors for fatal outcome among them. We reviewed 2 data sets of children <15 years admitted to the in-patient ward of the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr, b) with diarrhea and hypernatremia (serum sodium ≥150 mmol/L): (a) March 2001 to March 2002 (n = 371) and (b) March 2009 to August 2011 (n = 360). We reviewed their records and collected relevant information for analyses. The prevalence of hypernatremia was 5.1% (371/7212) and 2.4% (360/15 219), case fatality rate was 15% and 19%, respectively. In logistic regression analysis, the risk for death significantly increased in association with serum sodium ≥170 mmol/L, nutritional edema, hypoglycemia, respiratory distress, and absent peripheral pulses and reduced with the sole use of oral rehydration salts (ORS) or ORS following intravenous fluid, if indicated (for all, P < .05). Thus, managing children with hypernatremia using only ORS or ORS following intravenous fluid may help reduce the number of deaths.

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.

Factors Associated with Non-typhoidal Salmonella Bacteremia versus Typhoidal Salmonella Bacteremia in Patients Presenting for Care in an Urban Diarrheal Disease Hospital in Bangladesh.

BACKGROUND: Non-typhoidal Salmonella (NTS) and Salmonella enterica serovar Typhi bacteremia are the causes of significant morbidity and mortality worldwide. There is a paucity of data regarding NTS bacteremia in South Asia, a region with a high incidence of typhoidal bacteremia. We sought to determine clinical predictors and outcomes associated with NTS bacteremia compared with typhoidal bacteremia. METHODOLOGY: We performed a retrospective age-matched case-control study of patients admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between February 2009 and March 2013. We compared demographic, clinical, microbiological, and outcome variables of NTS bacteremic patients with age-matched S. Typhi bacteremic patients, and a separate comparison of patients with NTS bacteremia and patients with NTS gastroenteritis. PRINCIPAL FINDINGS: Of 20 patients with NTS bacteremia, 5 died (25% case fatality), compared to none of 60 age-matched cases of S. Typhi bacteremia. In univariate analysis, we found that compared with S. Typhi bacteremia, cases of NTS bacteremia had more severe acute malnutrition (SAM) in children under five years of age, less often presented with a duration of fever ≥ 5 days, and were more likely to have co-morbidities on admission such as pneumonia and clinical signs of sepsis (p<0.05 in all cases). In multivariable logistic regression, SAM, clinical sepsis, and pneumonia were independent risk factors for NTS bacteremia compared with S. Typhi bacteremia (p<0.05 in all cases). Notably, we found marked differences in antibiotic susceptibilities, including NTS strains resistant to antibiotics commonly used for empiric therapy of patients suspected to have typhoid fever. CONCLUSIONS/SIGNIFICANCE: Diarrheal patients with NTS bacteremia more often presented with co-morbidities and had a higher case fatality rate compared to those with typhoidal bacteremia. Clinicians in regions where both typhoid and NTS bacteremia are prevalent need to be vigilant about the possibility of both entities, especially given notable differences in antibiotic susceptibility patterns.

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.

The Prevalence of Mixed Helicobacter pylori Infections in Symptomatic and Asymptomatic Subjects in Dhaka, Bangladesh.

BACKGROUND: Helicobacter pylori is a highly genetically diverse bacterial species, which can persist in the gastric environment for decades. Recent studies have shown that single infections predominate in developed countries, whereas mixed infections are more prevalent in developing countries. Mixed infections of this bacterium may be important for adaptation to the hostile gastric environment and may facilitate dyspeptic symptoms. MATERIALS AND METHODS: To calculate the prevalence of mixed infections in symptomatic and asymptomatic subjects, 2010 H. pylori isolates collected from 83 symptomatic and 91 asymptomatic subjects from Dhaka, Bangladesh, were analyzed by (i) random amplified polymorphic DNA fingerprinting (RAPD) and (ii) multiplex PCR amplification for cagA and vacA virulence gene alleles. RESULTS: The overall prevalence of mixed H. pylori infection was 60.15% (77/128), indicating substantial co-colonization in this population. We additionally found that symptomatic subjects (53%) had a significantly higher rate of mixed infection than asymptomatic individuals (36.3%) (p = .016) and that the prevalence of the cagA and vacA and vacA m1/s1 and vacA m2/s1 alleles were higher in subjects with mixed infection. CONCLUSION: Our findings suggest that an increased diversity of the H. pylori strains in the gastric environment may contribute to the development of disease symptoms.

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.

Characteristics and predictors of death among hospitalized HIV-infected patients in a low HIV prevalence country: Bangladesh.

BACKGROUND: Predictors of death in hospitalized HIV-infected patients have not been previously reported in Bangladesh. OBJECTIVE: The primary aim of this study was to determine predictors of death among hospitalized HIV-infected patients at a large urban hospital in Bangladesh. METHODS: A study was conducted in the HIV in-patient unit (Jagori Ward) of icddr,b's Dhaka Hospital. Characteristics of patients who died during hospitalization were compared to those of patients discharged from the ward. Bivariate analysis was performed to determine associations between potential risk factors and death. Multivariable logistic regression was used to identify factors independently associated with death. RESULTS: Of 293 patients admitted to the Jagori Ward, 57 died during hospitalization. Most hospitalized patients (67%) were male and the median age was 35 (interquartile range: 2-65) years. Overall, 153 (52%) patients were diagnosed with HIV within 6 months of hospitalization. The most common presumptive opportunistic infections (OIs) identified were tuberculosis (32%), oesophageal candidiasis (9%), Pneumocystis jirovecii pneumonia (PJP) (8%), and histoplasmosis (7%). On multivariable analysis, independent predictors of mortality were CD4 count ≤200 cells/mm3 (adjusted odds ratio [aOR]: 16.6, 95% confidence interval [CI]: 3.7-74.4), PJP (aOR: 18.5, 95% CI: 4.68-73.3), oesophageal candidiasis (aOR: 27.5, 95% CI: 5.5-136.9), malignancy (aOR:15.2, 95% CI: 2.3-99.4), and bacteriuria (aOR:7.9, 95% CI: 1.2-50.5). Being on antiretroviral therapy prior to hospitalization (aOR: 0.2, 95% CI: 0.06-0.5) was associated with decreased mortality. CONCLUSION: This study showed that most patients who died during hospitalization on the Jagori Ward had HIV-related illnesses which could have been averted with earlier diagnosis of HIV and proper management of OIs. It is prudent to develop a national HIV screening programme to facilitate early identification of HIV.

Urban-rural differentials in overweight and obese individuals with diarrhea in bangladesh.

OBJECTIVE: The study aimed to determine urban and rural differences in overweight and obesity (OO) with diarrhea regarding subjects' sociodemographic, clinical characteristics, etiology, and antimicrobial susceptibility. METHODS: Relevant information from 2000 to 2011 were extracted from the data archive of the Diarrheal Disease Surveillance System of urban Dhaka (1248, 4.5%) and rural Matlab (615, 3.4%) hospitals of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b). RESULTS: The proportion of OO significantly increased in both urban (3-7%; chi-square for trend p < 0.001) and rural (1-6%; p < 0.001) areas over the study period. In multivariate modeling, monthly income more than US$100 (odds ratio [OR] = 54.44, 95% confidence interval [CI], 25.37-116.82, p < 0.001), high wealth quintile (OR = 18.23, 95% CI, 8.63-38.49, p < 0.001), access to sanitary toilet (OR = 3.07. 95% CI. 1.76-5.26. p < 0.001), boiled drinking water (OR = 2.77, 95% CI, 1.09-7.05, p = 0.032), antimicrobial use before hospitalization (OR = 4.99, 95% CI, 2.85-8.74, p < 0.001), fever (OR = 0.14, 95% CI, 0.37, 0.50, p < 0.001), watery stools (OR = 5.59, 95% CI, 2.11-14.80, p < 0.001), dehydrating diarrhea (OR = 5.17, 95% CI, 2.54-10.52, p < 0.001), intravenous saline infusion after hospitalization (OR = 2.65, 95% CI, 1.28-5.49, p = 0.009), and Salmonella infection (OR = 0.20, 95% CI, 0.50-0.83, p = 0.027) remained significantly associated with urban OO individuals. At least 88% of Shigella isolates were susceptible to ciprofloxacin in both urban and rural areas; for mecillinum it was 90%. Ciprofloxacin had the least detected resistance for Vibrio cholerae (0%) and trimethoprim-sulfamethoxazole (TMP-SMX) showed the greatest resistance (Dhaka 86%; Matlab 98%). Susceptibility for Salmonella showed ampicillin (95%), chloramphenecol (100%), ciprofloxacin (95%), ceftraxone (93%), TMP-SMX (95%) at both sites. CONCLUSION: Urban OO with diarrheal illnesses was significantly different from that in rural areas, including antimicrobial susceptibility.

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.

Changing characteristics of rotavirus diarrhea in children younger than five years in urban Bangladesh.

BACKGROUND: Childhood rotavirus diarrhea is still one of the major public health challenges. The present study aimed to determine changing characteristics of rotavirus diarrhea in under-5 children at two periods of time. METHODS: We enrolled 5,357 under-5 children with rotavirus positive in two different time periods; i) 1993-1997 (n = 2,493), and ii) 2008-2012 (n = 2,864) considering beginning and ending of two decades. These children were enrolled in the urban Dhaka Hospital of icddr,b. RESULTS: Overall, proportion of rotavirus was about 25% in 1993-97, which was 42% in 2008-12 (68% rise; p<0.001). Significant higher proportion of children were stunted [38% vs. 22%; aOR-1.33 (95% CI-1.09-1.62)], had vomiting [87% vs. 74%; aOR-2.58 (95% CI-2.02-3.28)], fever [10% vs. 8%; aOR-1.31 (95% CI-0.96-1.78)], family members >5 [38% vs. 35%; aOR-1.32 (95% CI-1.10-1.58)] required more intravenous fluid [9% vs. 3%; aOR-4.93 (95% CI-3.19-7.63)], had higher co-infection with Shigella [3% vs. 1%; aOR-3.36 (95% CI-1.61-7.03)], Vibrio cholerae [4% vs. 1%; aOR-3.70 (95% CI-2.12-6.46)]; and ETEC [13% vs. 7%; aOR-2.21 (95% CI-1.65-2.97)]; however, significantly lower proportion of them used sanitary toilets [54% vs. 78%; aOR-0.66 (95% CI-0.54-0.80)], boiled drinking water [16% vs. 38%; aOR-0.60 (95% CI-0.48-0.74)], used antimicrobial at home [63% vs. 82%; aOR-0.56 (95% CI-0.46-0.69)] and had some or severe dehydration [18% vs. 34%; aOR-0.15 (95% CI-0.12-0.20)] in 1st observation period compared to that of 2nd. CONCLUSION: Proportion of episodes of under-5 rotavirus diarrhea increased over the period. Concomitant changes in host, socio-demographic and clinical characteristics, and co-infections were also observed. Thus, vaccination campaign which is prevailing in private sector should also be introduced in public sector.