Long-term Impact of Changing Childhood Malnutrition on Rotavirus Diarrhoea: Two Decades of Adjusted Association with Climate and Socio-Demographic Factors from Urban Bangladesh

Background There is strong association between childhood rotavirus, diarrhoea, climate factors and malnutrition. Conversely, a significant nutritional transition (reduced under-nutrition) with a concurrent increasing trend of rotavirus infection in last decade was also observed among under 5 children, especially in developing countries including Bangladesh. Considering the pathophysiology of rotavirus, there might be an interaction of this nutrition transition which plays a pivotal role in increasing rotavirus infection in addition to climate and other man-made factors in urban areas such as Dhaka, Bangladesh. Methods Relevant monthly data from 1993–2012 were extracted from the archive of the Diarrhoeal Disease Surveillance System of icddr, b and linked with data collected from the Dhaka station of the Bangladesh Meteorological Department (mean temperature, rainfall, sea level pressure and humidity). Seasonal autoregressive integrated moving average time series models were deployed to determine the association between the monthly proportion of rotavirus infection and underweight, stunting and wasting adjusting for climate, socio-demographic and sanitation factors. Finding The proportion of rotavirus cases among all causes diarrhoea increased from 20% in 1993 to 43% in 2012 (Chi squared for trend p = 0.010). In contrast, underweight, stunting and wasting decreased from 59%-29% (p \u3c 0.001); 53%-21% (p \u3c 0.001) and 32%-22% (p \u3c 0.001) respectively over the same period. Mean ambient temperature increased from 25.76°C-26.62°C (p = 0.07); mean rainfall, sea level pressure and mean humidity decreased from 234.92–111.75 mm (p = 0.5), 1008.30–1006.61 mm of hg (p = 0.02) and 76.63%-70.26% (p \u3c 0.001), respectively. In the adjusted model, a decrease in monthly proportion of underweight [coef.: -0.189 (95% CI:-0.376, -0.003)] and wasting [-0.265 (-0.455, -0.075)] were significantly and inversely associated with rotavirus infection. However, an inverse but insignificant association was observed for stunting [-0.070 (-0.249, 0.109)]. Interpretation The reduction of acute childhood malnutrition is significantly associated with increasing rotavirus diarrhoea among under-5 children. Thus mass vaccination in addition to interventions directed at man-made modifiable predictors for prevention and control is warranted

Clinical characteristics, etiology and antimicrobial susceptibility among overweight and obese individuals with diarrhea: observed at a large diarrheal disease hospital, Bangladesh

Background:The present study aimed to determine the clinical characteristics and etiology of overweight and obese (OO) individuals with diarrhea attending an urban Dhaka Hospital, International Centre for Diarrheal Disease Research (icddr,b), Bangladesh.Methods:Total of 508 under-5 children, 96 individuals of 5-19 years and 1331 of >19 years were identified as OO from the Diarrheal Disease Surveillance System (DDSS) between 1993-2011. Two comparison groups such as well-nourished and malnourished individuals from respective age stratums were selected.Results:Isolation rate of rotavirus was higher among OO under-5 children compared to malnourished group (46% vs. 28%). Rotavirus infection among OO individuals aged 5-19 years (9% vs. 3%) (9% vs. 3%) and >19 years (6% vs. 4%) (6% vs. 3%) was higher compared to well-nourished and malnourished children. Conversely, Vibrio cholerae was lower among all OO age groups compared to well-nourished and malnourished ones. Shigella (4% vs. 6%) (4% vs. 8%), and Campylobacter (3% vs. 5%) (3% vs. 5%) were lower only among OO in >19 years individuals compared to their counterparts of the same age stratum. Salmonella was similarly isolated in all age strata and nutritional groups. In multinomial logistic regression among under-5 children, significant association was observed only with use of antimicrobials at home [OR-1.97] and duration of hospital stay [OR-0.68]. For individuals aged 5-19 years, use of antimicrobials at home (OR-1.83), some or severe dehydration (OR-3.12), having received intravenous saline (OR-0.46) and rotavirus diarrhea (OR-2.96) were found to be associated with OO respectively. Moreover, significant associations were also found for duration of diarrhea before coming to hospital (>24 hours) (OR-1.24), Shigella (OR-0.46), and Campylobacter (OR-0.58) among >19 years OO individuals along with other associated co-variates in 5-19 years group (all

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.publishedVersionPeer reviewe

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Real Time Analysis of Binding between Rituximab (Anti-CD20 Antibody) and B Lymphoma Cells

CD20, expressed on greater than 90% of B-lymphocytic lymphomas, is an attractive target for antibody therapy. Rituximab is a chimeric murine/human-engineered monoclonal antibody which can selectively deplete CD20-expressing cells in peripheral blood and lymphoid tissues. The immobilization of B-lymphoblast-like Burkitt’s lymphoma Raji cells on the quartz crystal microbalance (QCM) gold electrode surface using arginine–glycine–aspartic acid (RGD) tripeptide was electrochemically confirmed. The real-time processes of attachment of Raji cells on the gold electrode and the subsequent binding of Rituximab to the cells were studied using a QCM biosensor. The interaction between Rituximab and Raji cells led to the increased resonant frequency shifts (Δ<i>f</i>₀) in the studied antibody concentration range from 5 to 250 μg mL^–1 following the Langmuir adsorption model. From these observations, the apparent binding constant between a single-layer of Rituximab and Raji cells was calculated to be 1.6 × 10⁶ M^–1. Control experiments using other therapeutic antibodies (i.e., Trastuzumab and Bevacizumab) and different cells (i.e., T cells and endothelial cells) proved the specific interaction between Rituximab and B cells. The effects of Ca²⁺ and Mn²⁺ ions on the Rituximab–Raji cell interaction were also studied providing the enhanced QCM signals, in particular with Ca²⁺, further indicating that CD20 is a calcium ion channel that can transport these metal ions into the cells and accelerate the cell lysis induced by Rituximab. Thus, the real time capability of QCM and its simplicity of operation are shown to be highly suitable for multipurpose studies on living cells including cell-immobilization, cytotoxicity of drugs, and the cell action mechanisms

Factors Associated With Pneumonia Among Overweight and Obese Under-Five Children in an Urban Hospital of a Developing Country

To our knowledge, there are no data on the role of overweight and obesity in childhood pneumonia. We sought to determine that impact of overweight and obesity in such children. In this retrospective chart analysis, we enrolled hospitalized children aged 6 to 59 months in the Dhaka Hospital of the icddr,b, Bangladesh (International Centre for Diarrhoeal Disease Research, Bangladesh), from January 2010 to June 2014. Children with pneumonia having overweight and obesity (body mass index score [BMIZ] >2.00) constituted cases (n = 25), and those who had pneumonia without overweight and obesity (BMIZ -2.00 to 2.00) constituted controls (n = 75). Controls were 3-fold of the cases and were randomly selected. Demographic, clinical, and laboratory data of the cases and the controls were compared. The cases more often had diarrhea and dehydration (36% vs 12%, = .013), hypoxemia (SpO < 90% in room air; 28% vs 7%, = .009) on admission, and required to change antibiotics (32% vs 11%, = .023) during hospitalization compared to the controls. However, in logistic regression analysis the cases were independently associated with diarrhea ( < .001) and hypoxemia ( = .024) on admission. Our data suggest that overweight and obesity in children with pneumonia is prone to be associated with hypoxemia on admission, which may guide clinicians in promptly managing pneumonia in order to evade its ramification in such children. However, future research with larger samples is imperative to consolidate or refute our observation

Predictors of Death in Under-Five Children with Sepsis Attending an Urban Diarrheal Treatment Centre in Bangladesh

SETTING: Special Care Ward (SCW) of the Dhaka Hospital of icddr,b, Bangladesh. OBJECTIVE: To evaluate the clinical and laboratory predictors of death in under-five children with clinically defined sepsis presenting with diarrhea. METHODS: We prospectively enrolled all the diarrheal children (n = 151) aged 0 to 59 months with clinical sepsis admitted in the SCW during September’2007 through December’2007. Comparison was made between deaths (n = 23) and survivors (n = 128). Sepsis is defined as presence of inflammation [abnormal WBC count (>11 × 109/L or

Clinical and laboratory characteristics of children under five hospitalized with diarrhea and bacteremia.

BackgroundDiarrhea is one of the leading causes of mortality in children under five globally. When it is associated with bacteremia, mortality is even higher. However, bacteraemia in diarrheal children has gained little attention in spite of its deleterious impact in under-five mortality. So, we aimed to evaluate associated clinical and laboratory factors for death in under-five children hospitalized with both diarrhea and bacteremia.MethodsIn this retrospective cross-sectional study, we used patients' electronic database of Dhaka Hospital of 'icddr,b', and enrolled all under-five children with diarrhea and bacterial growth in their blood samples on admission between June-2014 and May-2017. Clinical and laboratory characteristics were compared between those who died and who survived with a special attention to bacterial pathogens related to deaths and their sensitivity pattern.ResultsIn a total of 401 diarrheal children with bacteraemia, 45 (11%) died. Although Salmonella Typhi (34%) was the most predominant isolate followed by Staphylococcus species (16%) and Pseudomonas species (9%), children who died more often had E. coli (OR = 5.69, 95% CI = 2.42-13.39, p = Conclusion and significanceThe results of our data suggest that diarrheal children with bacteremia who died more often had gram negative bacteremia compared to those who survived and these pathogens are highly resistant to WHO recommended first line and second line antibiotics. The results further emphasize the critical importance of early identification of important clinical problems such as clinical sepsis, hypoxemia and hyperkalaemia in diarrheal children and treat them with potential sensitive antibiotic(s) in order to reduce bacteremia related mortality in children with diarrhea, especially in resource limited settings