Characteristics and outcomes of children 2-23 months of age with prolonged diarrhoea: A secondary analysis of data from the 'Antibiotics for Children with Diarrhea' trial.

Background: Approximately 12% of all diarrhoeal episodes last for 7-13 days. As such, they are termed prolonged diarrhoea, and are associated with over two-thirds of all diarrhoeal deaths. Due to a lack of robust data, we aimed to evaluate a comparative background characteristics of young children with acute and prolonged diarrhoea, and their outcomes at day 90 follow-up. Methods: We performed a secondary analysis of data from the Antibiotics for Children with Diarrhea (ABCD) trial. Children aged 2-23 months were enrolled between July 2017 and July 2019 from seven Asian and sub-Saharan African countries. For this analysis, we divide diarrhoea into two categories: acute diarrhoea (duration <7 days) and prolonged diarrhoea (duration ≥7-13 days). We used logistic regression to observe baseline crude and adjusted associations and linear regression to compare post-discharge outcomes. Results: We analysed data on 8266 children, of whom 756 (9%) had prolonged diarrhoea and 7510 (91%) had acute diarrhoea. Pakistan had the highest proportion of children with prolonged diarrhoea (n/N = 178/1132, 16%), while Tanzania had the lowest (n/N = 12/1200, 1%). From an analysis that adjusted for sex, breastfeeding, nutritional status, clinical presentation, housing, water supply, sanitation, and country, we observed that presentation at a health facility with prolonged diarrhoea was associated with low age (2-12 months) (adjusted odds ratio (aOR) = 1.25; 95% confidence interval (CI) = 1.02, 1.53; P = 0.028), presence of three or more under-five children in the family (aOR = 1.54; 95% CI = 1.26, 1.87; P < 0.001), maternal illiteracy (aOR = 1.45; 95% CI = 1.21, 1.74, P < 0.001), moderate underweight (aOR = 1.25; 95% CI = 1.01, 1.55; P = 0.042) and pathogen (Campylobacter) (aOR = 1.27; 95% CI = 1.12, 1.44; P < 0.001). At day 90 follow-up, children with prolonged diarrhoea had significantly lower weight-for-age z-score compared to children with acute diarrhoea (-1.62, standard deviation (SD) = 1.11 vs -1.52, SD = 1.20; P = 0.032), as well as significantly higher frequency of hospital admission (6.1% vs 4.5%; P = 0.042). Conclusions: Prolonged diarrhoea was more common in children of younger age, those who were moderately underweight, those with Campylobacter in stool, those with three or more under-five children in a family, and those with illiterate mothers compared to those who had acute diarrhoea. Children with prolonged diarrhoea more often required hospitalisation during the three-month follow-up period compared to their counterparts.

Derivation and validation of a clinical prediction model for risk-stratification of children hospitalized with severe pneumonia in Bangladesh.

Children with severe pneumonia in low- and middle-income countries (LMICs) suffer from high rates of treatment failure despite appropriate World Health Organization (WHO)-directed antibiotic treatment. Developing a clinical prediction rule for treatment failure may allow early identification of high-risk patients and timely intervention to decrease mortality. We used data from two separate studies conducted at the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) to derive and externally validate a clinical prediction rule for treatment failure of children hospitalized with severe pneumonia. The derivation dataset was from a randomized clinical trial conducted from 2018 to 2019, studying children aged 2 to 59 months hospitalized with severe pneumonia as defined by WHO. Treatment failure was defined by the persistence of danger signs at the end of 48 hours of antibiotic treatment or the appearance of any new danger signs within 24 hours of enrollment. We built a random forest model to identify the top predictors. The top six predictors were the presence of grunting, room air saturation, temperature, the presence of lower chest wall indrawing, the presence of respiratory distress, and central cyanosis. Using these six predictors, we created a parsimonious model with a discriminatory performance of 0.691, as measured by area under the receiving operating curve (AUC). We performed external validation using a temporally distinct dataset from a cohort study of 191 similarly aged children with severe acute malnutrition and pneumonia. In external validation, discriminatory performance was maintained with an improved AUC of 0.718. In conclusion, we developed and externally validated a parsimonious six-predictor model using random forest methods to predict treatment failure in young children with severe pneumonia in Bangladesh. These findings can be used to further develop and validate parsimonious and pragmatic prognostic clinical prediction rules for pediatric pneumonia, particularly in LMICs.

Features and risk factors of post-COVID-19 syndrome: findings from a longitudinal study in Bangladesh.

Background: A comprehensive study of the post-COVID syndrome (PCS) remains scarce in low-and middle-income countries. We assessed the prevalence, incidence rate, evolution over time, and risk factors of PCS among hospitalized (HS) and non-hospitalized (NHS) COVID-19 survivors. Methods: We undertook a prospective longitudinal study of COVID-19 survivors at months 1, 3, and 5 post-discharge or post-isolation period. The study was conducted at two COVID-19-designated hospitals in Dhaka, Bangladesh, between December 2020 and October 2021. Findings: 362 participants were enrolled in the study; the median time from the onset of COVID-19 to enrolment was 57 days (IQR 41, 82). At enrolment, after adjusting for potential confounders, the HS more often had one or more symptoms, peripheral neuropathy (PN), depression and anxiety disorder, poor quality of life, dyspnea, tachycardia, restrictive lung disease on spirometry, anemia, proteinuria, and need for insulin therapy than the non-hospitalized group (95% CI > 1 for all). Although most of these findings decreased significantly over time in HS, PN increased in both groups. The incidence of diabetes was 9.8/1000 person-month, and the new requirement of insulin therapy was higher (aOR, 6.71; 95% CI, 2.87, 15.67) among HS than the NHS. Older age, being female, comorbidity, cigarette smoking, hospitalization, and contact with COVID-19 cases were independently associated with PCS. Interpretation: We observed a high burden of PCS in hospitalized and non-hospitalized survivors despite most findings' decreasing trend over time. Our results underscore the importance of continuing long-term follow-up and subsequent management. Funding: The United States Agency for International Development (USAID).

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.

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.

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.

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.

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.

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.

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.

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.