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

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

Vaccination following the expanded programme on immunization schedule could help to reduce deaths in children under five hospitalized for pneumonia and severe pneumonia in a developing country.

Background: Worldwide, pneumonia is the leading cause of mortality in children under the age of five. An expanded program on immunization (EPI) is one kind of evidence-based tool for controlling and even eradicating infectious diseases. Objectives: This study aimed to explore the impact of EPI vaccination, including BCG, DPT-Hib-Hep B, OPV, IPV, and PCV-10, among children from the age of 4 to 59 months hospitalized for pneumonia and severe pneumonia. Additionally, we evaluated the role of 10 valent pneumococcal conjugate vaccines alone on clinical outcomes in such children. Methods: In this retrospective chart review, children from the age of 4 to 59 months with WHO-defined pneumonia and severe pneumonia admitted to the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017 who had the information on immunization as per EPI schedule by 4 months of age were included in the analysis. A comparison was made between the children who were fully immunized (immunization with BCG, DPT-Hib-Hep B, OPV, and IPV from 2013 to 2015 and PCV-10 from 2015 to 2017) and who were not immunized (consisting of partial immunization and no immunization) during the study period. Results: A total of 4,625 children had pneumonia and severe pneumonia during the study period. Among them, 2,605 (56.3%) had received the information on immunization; 2,195 (84.3%) were fully immunized by 4 months of age according to the EPI schedule and 410 were not immunized. In the log-linear binomial regression analysis, immunization of children from 4 to 59 months of age was found to be associated with a lower risk of diarrhea (p = 0.033), severe pneumonia (p = 0.001), anemia (p = 0.026), and deaths (p = 0.035). Importantly, the risk of developing severe pneumonia (1054/1,570 [67%] vs. 202/257 [79%], p < 0.001) and case-fatality rate (57/1,570 [3.6%] vs. 19/257 [7.4%], p = 0.005) was still significantly lower among those who were immunized with PCV-10 than those who were not. Conclusion: Children immunized as per the EPI schedule were at a lower risk of diarrhea, severe pneumonia, anemia, and death, compared to unvaccinated children. In addition, PCV-10 was found to be protective against severe pneumonia and deaths in vaccinated children. The overall results underscored the importance of the continuation of immunization, scrupulously adhering to the EPI schedule to reduce the risk of morbidities and mortalities in children, especially in resource-limited settings.

In-person training on COVID-19 case management and infection prevention and control: Evaluation of healthcare professionals in Bangladesh.

BACKGROUND: As COVID-19 was declared a global pandemic, the major focus of healthcare organizations shifted towards preparing healthcare systems to handle the inevitable COVID-19 burden at different phases and levels. A series of in-person training programs were operated in collaboration with government and partner organizations for the healthcare workers (HCW) of Bangladesh. This study aimed to assess the knowledge of HCWs regarding SARS-CoV-2 infection, their case management, infection prevention and control to fight against the ongoing pandemic. METHODS: As a part of the National Preparedness and Response Plan for COVID-19 in Bangladesh, the training program was conducted at four district-level hospitals and one specialized hospital in Bangladesh from July 1, 2020 to June 30, 2021. A total of 755 HCWs participated in the training sessions. Among them, 357 (47%) were enrolled for the evaluation upon completion of the data, collected from one district hospital (Feni) and one specialized hospital (National Institute of Mental Health). RESULTS: The mean percentage of pre-test and post-test scores of all the participants were found to be 57% (95% CI 8.34-8.91; p 0.01) and 65% (95% CI 9.56-10.15; p <0.001) respectively. The difference of score (mean) between the groups was significant (p<0.001). After categorizing participants' knowledge levels as poor, average and fair, doctors' group has shown to have significant enhancement from level of average to fair compared to that of the nurses. Factors associated with knowledge augmentation of doctors were working in primary health care centers (aOR: 4.22; 95% CI: 1.80, 9.88), job experience less than 5 years (aOR: 4.10; 95% CI: 1.01, 16.63) and experience in caring of family member with COVID-19 morbidity (aOR: 2.06; 95% CI: 1.03, 4.10), after adjusting for relevant covariates such as age, sex and prior COVID-19 illness. CONCLUSION: Considering the series of waves of COVID-19 pandemic with newer variants, the present paper underscores the importance of implementing the structured in-person training program on case management, infection prevention and control for the HCWs that may help for successful readiness prior to future pandemics that may further help to minimize the pandemic related fatal consequences.

Prevalence and outcome of anemia among children hospitalized for pneumonia and their risk of mortality in a developing country.

Data are limited on the prevalence and outcome of anemia and its risk on mortality among children under five years of age hospitalized for pneumonia/severe pneumonia. Thus, we conducted a secondary analysis of data extracted from Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh to address the evidence gap. Among 3468 children fulfilling the study criteria,1712 (49.4%) had anemia. If children aged ≤ 1.0, > 1.0 to 2.0, > 2.0 to < 6.0, and ≥ 6.0 to 59 months had blood hemoglobin (Hb) value of ≤ 10.7 g/dL, ≤ 9.4 g/dL, ≤ 9.5 g/dL, and ≤ 11 g/dl respectively; we considered them anemic. The trend of prevalence of anemia was found to be inversely related to increasing age (Chi-square for linear trend analysis was done to understand the relation of anemia with increasing age, which was = 6.96; p = 0.008). During hospitalization anemic children more often developed respiratory failure (7.2% vs. 4.4%, p < 0.001) and fatal outcome (7.1.0% vs. 4.2%, p < 0.001) than the children who did not have anemia. After adjusting for potential confounders, such as female sex, lack of immunization, abnormal mental status, severe acute malnutrition, dehydration, hypoxemia, severe sepsis, and bacteremia using multivariable logistic regression analysis, anemia was found to be independently associated with fatal outcome (OR = 1.88, 95% CI 1.23-2.89, p = 0.004). Thus, future interventional studies on the early management of anemia may be warranted to understand whether the intervention reduces the morbidity and deaths in such children.

Prevalence, Predictive Factors, and Outcomes of Respiratory Failure in Children With Pneumonia Admitted in a Developing Country.

Background: Pneumonia has been the leading infectious cause of morbidity and mortality in children under 5 years of age for the last several decades. Although most of these deaths occur due to respiratory failure, published data are limited regarding predicting factors and outcomes of respiratory failure in children hospitalized with pneumonia or severe pneumonia. Objective: This study aimed to explore the prevalence, predicting factors, and outcomes of respiratory failure in children under-five with pneumonia or severe pneumonia. Methods: In this retrospective chart analysis, we enrolled children under 5 years of age hospitalized with pneumonia or severe pneumonia in the Dhaka Hospital of International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) between August 2013 and December 2017. Comparisons were made between children with respiratory failure (n = 212) and those without respiratory failure (n = 4,412). Respiratory failure was defined when the oxygen saturation/fraction of inspired oxygen (SpO2/FiO2) was <315. Results: A total of 4,625 children with pneumonia or severe pneumonia were admitted during this study period. Among them, 212 (4.6%) children developed respiratory failure and formed the case group. A total of 4,412 (95.3%) children did not develop respiratory failure and formed the comparison group. In logistic regression analysis, after adjusting with potential confounders, severe sepsis [adjusted odds ratio (aOR): 12.68, 95% CI: 8.74-18.40], convulsion (aOR: 4.52, 95% CI: 3.06-6.68), anemia (aOR: 1.76, 95% CI: 1.20-2.57), and severe underweight (aOR: 1.97, 95% CI: 1.34-2.89) were found to be independently associated with respiratory failure. As expected, children with respiratory failure more often had fatal outcome than without respiratory failure (74, 1%, p < 0.001). Conclusion: The results of our analyses revealed that prevalence of respiratory failure was 4.6% among under-five children hospitalized for pneumonia or severe pneumonia. Severe sepsis, convulsion, anemia, and severe underweight were the independent predictors for respiratory failure in such children and their case-fatality rate was significantly higher than those without respiratory failure. Early recognition of these predicting factors of respiratory failure may help clinicians imitating prompt treatment that may further help to reduce deaths in such children, especially in resource-limited settings.

Physical Quality of Life of Sepsis Survivor Severely Malnourished Children after Hospital Discharge: Findings from a Retrospective Chart Analysis.

BACKGROUND: Quality of life (QoL) among pediatric sepsis survivors in resource-limited countries is poorly understood. We aimed to evaluate the QoL among sepsis survivors, by comparing them with non-sepsis survivors three months after hospital discharge. METHODOLOGY: In this retrospective chart analysis with a case-control design, we compared children having sepsis and non-sepsis at hospital admission and during their post-hospitalization life, where the study population was derived from a hospital cohort of 405 severely malnourished children having pneumonia. RESULTS: The median age (months, inter-quartile range) of the children having sepsis and non-sepsis was 10 (5, 17) and 9 (5, 18), respectively. Approximately half of the children among the sepsis survivors had new episodes of respiratory symptoms at home. Though death was significantly higher (15.8% vs. 2.7%, p ≤ 0.001) at admission among the sepsis group, deaths during post-hospitalization life (7.8% vs. 8.8%, p = 0.878) were comparable. A verbal autopsy revealed that before death, most of the children from the sepsis group had respiratory complaints, whereas gastrointestinal complaints were more common among the non-sepsis group. CONCLUSIONS: Pediatric sepsis is life-threatening both during hospitalization and post-discharge. The QoL after sepsis is compromised, including re-hospitalization and the development of new episodes of respiratory symptoms especially before death.

Toxoplasma gondii Infection Is Associated with Low Birth Weight: Findings from an Observational Study among Rural Bangladeshi Women.

Gestational Toxoplasma gondii (T. gondii) infection may cause substantial adverse effects on developing fetuses, newborns and also mothers. This study aims to estimate the seroprevalence of T. gondii among rural Bangladeshi pregnant women and determine the risk of a low birth weight (LBW). We followed a longitudinal design where 208 pregnant women were followed until the birth of their infants. Levels of IgG and IgM of T. gondii were assessed using chemiluminescent immunoassay. Modified Poisson regression was used to estimate crude and adjusted associations and multiple regression analysis was performed to understand the confounding and modifying effects of the variables. Thirty-nine (19%) children were born with LBW, among whom 15 (39%) mothers were positive for T. gondii IgG during pregnancy. After adjusting for several confounders and modifiers, pregnant women with T. gondii IgG or IgM seropositivity were significantly associated with LBW of infants (aRR: 2.00, 95% CI: 1.17-3.42). The strength of this association increased after adjusting for maternal education (aRR: 4.88, 95% CI: 1.74-13.69). The final model had an AROC of 0.84 with a sensitivity of 36% and specificity of 97%. Although causality is yet to be established, the study observed an association between T. gondii infection during pregnancy among rural Bangladeshi women and LBW of newborns.

Characteristics of severely malnourished under-five children immunized with Bacillus Calmette-Guérin following Expanded Programme on Immunization schedule and their outcomes during hospitalization at an urban diarrheal treatment centre, Bangladesh.

BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination has recently been found to have beneficial effects among children infected other than Mycobacterium tuberculosis. Due to the paucity of data on the outcomes of children who had successful BCG vaccination following Expanded Programme on Immunization (EPI) schedule, we aimed to investigate the characteristics of such children and their outcomes who were hospitalized for severe malnutrition. METHODS: A prospective observational study was conducted to determine the viral etiology of pneumonia in severely malnourished children those were admitted to the Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between April 2015 and December 2017, constituted the study population. Using a case-control design for the analysis, children having BCG vaccination prior hospital admission were treated as cases (n = 611) and those without vaccination, constituted as controls (n = 83). Bi-variate analysis was conducted using socio-demographic, clinical, laboratory, and treatment characteristics on admission and outcomes during hospitalization. Finally, log-linear binomial regression analysis was done to identify independent impact of BCG vaccination. RESULTS: The cases more often presented with older age, have had lower proportion of maternal illiteracy, higher rate of breastfeeding, severe wasting and lower rate of hypoglycemia, compared to the controls. The cases were also found to have lower risk of severe sepsis and deaths, compared to the controls (for all, p<0.05). However, in log-linear binomial regression analysis, after adjusting for potential confounders, BCG vaccination following EPI schedule (RR:0.54; 95%CI = 0.33-0.89; p = 0.015) and breastfeeding (RR:0.53; 95%CI = 0.35-0.81; p = 0.003) were found to be protective for the development of severe sepsis. CONCLUSION: BCG vaccination and breastfeeding were found to be protective for the development of severe sepsis in hospitalized severely malnourished under-five children which underscores the importance of continuation of BCG vaccination at birth and breastfeeding up to two years of age.

Effect of 3 Days of Oral Azithromycin on Young Children With Acute Diarrhea in Low-Resource Settings: A Randomized Clinical Trial.

Importance: World Health Organization (WHO) guidelines do not recommend routine antibiotic use for children with acute watery diarrhea. However, recent studies suggest that a significant proportion of such episodes have a bacterial cause and are associated with mortality and growth impairment, especially among children at high risk of diarrhea-associated mortality. Expanding antibiotic use among dehydrated or undernourished children may reduce diarrhea-associated mortality and improve growth. Objective: To determine whether the addition of azithromycin to standard case management of acute nonbloody watery diarrhea for children aged 2 to 23 months who are dehydrated or undernourished could reduce mortality and improve linear growth. Design, Setting, and Participants: The Antibiotics for Children with Diarrhea (ABCD) trial was a multicountry, randomized, double-blind, clinical trial among 8266 high-risk children aged 2 to 23 months presenting with acute nonbloody diarrhea. Participants were recruited between July 1, 2017, and July 10, 2019, from 36 outpatient hospital departments or community health centers in a mixture of urban and rural settings in Bangladesh, India, Kenya, Malawi, Mali, Pakistan, and Tanzania. Each participant was followed up for 180 days. Primary analysis included all randomized participants by intention to treat. Interventions: Enrolled children were randomly assigned to receive either oral azithromycin, 10 mg/kg, or placebo once daily for 3 days in addition to standard WHO case management protocols for the management of acute watery diarrhea. Main Outcomes and Measures: Primary outcomes included all-cause mortality up to 180 days after enrollment and linear growth faltering 90 days after enrollment. Results: A total of 8266 children (4463 boys [54.0%]; mean [SD] age, 11.6 [5.3] months) were randomized. A total of 20 of 4133 children in the azithromycin group (0.5%) and 28 of 4135 children in the placebo group (0.7%) died (relative risk, 0.72; 95% CI, 0.40-1.27). The mean (SD) change in length-for-age z scores 90 days after enrollment was -0.16 (0.59) in the azithromycin group and -0.19 (0.60) in the placebo group (risk difference, 0.03; 95% CI, 0.01-0.06). Overall mortality was much lower than anticipated, and the trial was stopped for futility at the prespecified interim analysis. Conclusions and Relevance: The study did not detect a survival benefit for children from the addition of azithromycin to standard WHO case management of acute watery diarrhea in low-resource settings. There was a small reduction in linear growth faltering in the azithromycin group, although the magnitude of this effect was not likely to be clinically significant. In low-resource settings, expansion of antibiotic use is not warranted. Adherence to current WHO case management protocols for watery diarrhea remains appropriate and should be encouraged. Trial Registration: ClinicalTrials.gov Identifier: NCT03130114.

Risk Factors and Outcomes of Hospital Acquired Pneumonia in Young Bangladeshi Children.

Hospital acquired pneumonia (HAP) is common and often associated with high mortality in children aged five or less. We sought to evaluate the risk factors and outcome of HAP in such children. We compared demographic, clinical, and laboratory characteristics in children <5 years using a case control design during the period of August 2013 and December 2017, where children with HAP were constituted as cases (n = 281) and twice as many randomly selected children without HAP were constituted as controls (n = 562). HAP was defined as a child developing a new episode of pneumonia both clinically and radiologically after at least 48 h of hospitalization. A total of 4101 children were treated during the study period. The mortality was significantly higher among the cases than the controls (8% vs. 4%, p = 0.014). In multivariate logistic regression analysis, after adjusting for potential confounders, it was found that persistent diarrhea (95% CI = 1.32-5.79; p = 0.007), severe acute malnutrition (95% CI = 1.46-3.27; p < 0.001), bacteremia (95% CI = 1.16-3.49; p = 0.013), and prolonged hospitalization of >5 days (95% CI = 3.01-8.02; p < 0.001) were identified as independent risk factors for HAP. Early identification of these risk factors and their prompt management may help to reduce HAP-related fatal consequences, especially in resource limited settings.

Vibrio cholerae O139 persists in Dhaka, Bangladesh since 1993.

BACKGROUND: After a multi-country Asian outbreak of cholera due to Vibrio cholerae serogroup O139 which started in 1992, it is rarely detected from any country in Asia and has not been detected from patients in Africa. METHODOLOGY/PRINCIPAL FINDINGS: We extracted surveillance data from the Dhaka and Matlab Hospitals of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) to review trends in isolation of Vibrio cholerae O139 in Bangladesh. Data from the Dhaka Hospital is a 2% sample of > 100,000 diarrhoeal patients treated annually. Data from the Matlab Hospital includes all diarrhoeal patients who hail from the villages included in the Matlab Health and Demographic Surveillance System. Vibrio cholerae O139 was first isolated in Dhaka in 1993 and had been isolated every year since then except for a gap between 2005 and 2008. An average of thirteen isolates was detected annually from the Dhaka Hospital during the last ten years, yielding an estimated 650 cases annually at this hospital. During the last ten years, cases due to serogroup O139 represented 0.47% of all cholera cases; the others being due to serogroup O1. No cases with serogroup O139 were identified at Matlab since 2006. Clinical signs and symptoms of cholera due to serogroup O139 were similar to cases due to serogroup O1 though more of the O139 cases were not dehydrated. Most isolates of O139 remained sensitive to tetracycline, ciprofloxacin, and azithromycin, but they became resistant to erythromycin starting in 2009. CONCLUSIONS/SIGNIFICANCE: Cholera due to Vibrio cholerae serogroup O139 continues to cause typical cholera in Dhaka, Bangladesh.

Implementation of the 2017 American College of Cardiology/American Heart Association Guidelines on Hypertension in Clinical Practice.

Background: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on hypertension recommend a threshold blood pressure (BP) of ≥130/80 mmHg for diagnosis of hypertension and treating hypertension to a goal BP of <130/80 mmHg. For this study, we assessed the rate of compliance to the 2017 ACC/AHA hypertension guidelines by internal medicine residents and cardiology fellows in clinics affiliated with a teaching hospital in New York, New York. Methods: We conducted a retrospective medical records review for patients who had a clinical encounter at the internal medicine resident and cardiology fellow clinics from January to February 2019. To distinguish from adherence with prior guidelines, patients with BP of 130-139/80-89 mmHg (unless age ≥60 years and systolic blood pressure [SBP] 140-149 mmHg without chronic kidney disease or diabetes) were included. The primary outcome was accurate assessment of uncontrolled BP in accordance with the 2017 ACC/AHA guidelines. Results: Included in the analysis were 435 patients from the internal medicine resident clinic and 127 patients from the cardiology fellow clinic. Accurate assessment of uncontrolled BP was higher in the cardiology fellow clinic compared to the internal medicine resident clinic (29.1% vs 10.3%, P<0.001), even after adjusting for baseline characteristics differences between the 2 clinics. Multivariate regression analysis revealed that the type of clinic (internal medicine, odds ratio [OR] 0.27, 95% CI 0.16-0.47; P<0.001), established diagnosis of hypertension (OR 2.06, 95% CI 1.06-3.99; P<0.001), and SBP (OR 1.16 per mmHg, 95% CI 1.11-1.22; P=0.031) were independently associated with the primary outcome. Conclusion: Cardiology fellows were better at identifying hypertension diagnosis thresholds and BP treatment goals in accordance with 2017 ACC/AHA guidelines compared to internal medicine residents.

Factors associated with severe sepsis in diarrheal adults and their outcome at an urban hospital, Bangladesh: A retrospective analysis.

BACKGROUND: To describe factors associated with severe sepsis in diarrheal adults and their outcomes and offender in blood and stool to understand their interplay as clinical features of sepsis and severe diarrhea often overlap. METHODS AND RESULTS: We used this retrospective chart analysis employing an unmatched case-control design to study critically ill diarrheal adults aged ≥18 years treated in ICU of Dhaka hospital, icddr,b between January 2011 to December 2015. Of 8,863 in-patient diarrheal adults, 350 having severe sepsis were cases and an equal number of randomly selected non-septic patients were the controls. Cases died significantly more (14.9% vs 4.6%, p = <0.001) than controls. 69% of the cases progressed to septic shock. In logistic regression analysis, steroid intake, ileus, acute kidney injury (AKI), metabolic acidosis, and hypocalcemia were significantly associated with severe sepsis in diarrheal adults (all, p<0.05). 12% of cases (40/335) had bacteremia. Streptococcus pneumoniae [9 (22.5%)] was the single most common pathogen and gram-negatives [27 (67.5%)] were prevailing as a group. CONCLUSION: Diarrheal adults who had ileus, AKI, metabolic acidosis, hypocalcemia, and also took steroids were found to have an association with severe sepsis. Strikingly, gram-negative were the predominant bacteria among the diarrheal adults having severe sepsis.

Seizure in Children Under Five Presenting With Pneumonia in a Critical Care Ward in Bangladesh: Prevalence, Associated Factors, and Outcome.

BACKGROUND: Pneumonia is the leading infectious cause of deaths in children under 5 for the last few decades. Development of seizure in those children is common and associated with increased risk of deaths. We therefore investigated the prevalence, associated factors and outcome of seizure in children hospitalized with pneumonia. METHODS: We conducted a retrospective chart analysis in the intensive care unit of the Dhaka Hospital of icddr,b. Children under 5 with World Health Organization (WHO) classified clinical (excluding seizure as 1 of the clinical diagnostics) and radiologic pneumonia, admitted to the intensive care unit at Dhaka Hospital of icddr,b between August 2013 and December 2017 were analyzed. We initially identified the children with pneumonia who had seizure. For comparison, we have taken 2 folds randomly selected controls from rest of the children with pneumonia having no seizure. Prevalence and outcome of children with pneumonia and seizure were measured. Factors associated with seizure in children with pneumonia compared with those without seizure were also identified. Seizure was characterized by sudden, violent, involuntary, and abnormal repetitive movements with or without loss or impairment of consciousness confirmed by attending physician. RESULTS: Among a total of 4101 children with pneumonia, 514 (12.5%) had seizure. Compared with children with pneumonia alone children having pneumonia and seizure more often developed respiratory failure (18% vs. 3%, P < 0.001) and died (13% vs. 3%, P < 0.001) during hospitalization. In logistic regression analysis hypoxemia (95% CI: 1.59-3.17, P < 0.001), severe pneumonia (95% CI: 2.13-6.52, P < 0.001), severe sepsis (95% CI: 1.30-2.88, P = 0.001), and hypernatremia (95% CI: 5.31-10.93, P < 0.001) were found to be independent risk factors for seizure. On the contrary, children with pneumonia having seizure were less likely to have severe acute malnutrition (95% CI: 0.26-0.50, P < 0.001). CONCLUSIONS: Early identification of risk factors for seizure in children with pneumonia may be helpful for clinicians to promptly treat them and therefore may have potential to reduce deaths in those children especially in resource limited settings.

Factors Associated with Congenital Heart Disease in Severely Malnourished Children under Five and Their Outcomes at an Urban Hospital, Bangladesh.

Congenital heart disease (CHD) is one of the most common types of birth defect with a high morbidity and mortality, particularly in severely malnourished children under five. In this study, we aim to identify the predicting factors for CHD and their outcomes. 694 malnourished children under five years of age admitted between April 2015 and December 2017 constituted the study population. Of them, 64 were cases of CHD, and by comparison 630 were without CHD. CHD was diagnosed clinically and confirmed by echocardiogram. 64% of the cases had a single defect. Cases were more likely to be present with diarrhea, cough, respiratory distress, cyanosis, hypoxemia, hypoglycemia and hypernatremia on admission. The cases also had a high proportion of severe sepsis, bacteremia, heart failure, respiratory failure and death, compared to those without CHD. Cough (95% CI = 1.09-18.92), respiratory distress (95% CI = 1.46-5.39) and hypoxemia (95% CI = 1.59-6.86) were found to be the independent predictors for CHD after regression analysis, and their early identification might be helpful to lessen ramifications, including mortality, in such populations, especially in resource-limited settings.

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

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

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

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

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

Changing Susceptibility Pattern of Vibrio cholerae O1 Isolates to Commonly Used Antibiotics in the Largest Diarrheal Disease Hospital in Bangladesh during 2000-2018.

The efficacy of commonly used antibiotics for treating severe cholera has been compromised over time because of the reduced antibiotic susceptibility. This study aimed to describe the rate of detection of Vibrio cholerae O1 from fecal samples and antimicrobial susceptibility profiles of V. cholerae O1 serotypes to commonly used antibiotics. During January 2000-December 2018, V. cholerae O1 was detected in fecal samples of 7,472 patients. Vibrio cholerae O1 Inaba serotype was predominant, ranging from 60% to 86% during the period 2000-2006 except for 2003 and 2005 when the Ogawa serotype was predominant. Later on, the Ogawa serotype became predominant from 2007 to 2015, fluctuating between 52% and 100%. However, in 2016 and 2017, isolation rates declined to 2% and 1%, respectively, but surged again to 75% in 2018. Nearly 100% of V. cholerae O1 strains were sensitive to tetracycline during 2000-2004. Thereafter, a declining trend of sensitivity was observed to be continued and dropped down to < 6% during 2012-2017 and again increased to 76% in 2018. Susceptibility to azithromycin and ciprofloxacin was nearly 100%, and susceptibility to cotrimoxazole and furazolidone was 01% throughout the study period. We also found the emergence of resistance to erythromycin in 2005 and sensitivity to cotrimoxazole in 2018. Thus, the rapid decline of the sensitivity of V. cholerae O1 to tetracycline and a reversed peak after 6 years need continued monitoring and reporting.

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

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

Predictor of Death in Diarrheal Children Under 5 Years of Age Having Severe Sepsis in an Urban Critical Care Ward in Bangladesh.

We aimed to identify clinical predictors of fatal outcome in children under 5 years of age having diarrhea and severe sepsis and treated in the Intensive Care Unit of the Dhaka Hospital of icddr,b from October 2010 through September 2011. Among 191 enrolled children, 70 (37%) died and were considered to be cases, while the remaining 121 (63%) who survived constituted the controls. The cases more often had shortness of breath (SOB), septic shock, dehydrating diarrhea compared with the controls (for all, P < .05). After adjusting for potential confounders using logistic regression analysis, the likelihood of death was higher in children who had septic shock and SOB and lower in children having dehydrating diarrhea (for all, P < .05). Thus, SOB can trigger an early alarm for sepsis recognition; otherwise, these children can end up with fatality from septic shock. In resource-poor settings, early identification of these predictors can alleviate death.