Vibrio cholerae in rural and urban Bangladesh, findings from hospital-based surveillance, 2000–2021

With more than 100,000 cases estimated each year, Bangladesh is one of the countries with the highest number of people at risk for cholera. Moreover, Bangladesh is formulating a countrywide cholera-control plan to satisfy the GTFCC (The Global Task Force on Cholera Control) Roadmap\u27s goals. With a particular focus on cholera trends, variance in baseline and clinical characteristics of cholera cases, and trends in antibiotic susceptibility among clinical isolates of Vibrio cholerae, we used data from facility-based surveillance systems from icddr,b’s Dhaka, and Matlab Hospitals from years 2000 to 2021. Female patients comprised 3,553 (43%) in urban and 1,099 (51.6%) in rural sites. Of the cases and most patients 5,236 (63.7%) in urban and 1,208 (56.7%) in the rural site were aged 15 years and more. More than 50% of the families belonged to the poor and lower-middle-class; in 2009 (24.4%) were in urban and in 1,791 (84.2%) were in rural sites. In the urban site, 2,446 (30%) of households used untreated drinking water, and 702 (9%) of families disposed of waste in their courtyard. In the multiple logistic regression analysis, the risk of cholera has significantly increased due to waste disposal in the courtyard and the boiling of water has a protective effect against cholera. Rotavirus (9.7%) was the most prevalent co-pathogen among the under-5 children in both sites. In urban sites, the percentage of V. cholerae along with co-existing ETEC and Campylobacter is changing in the last 20 years; Campylobacter (8.36%) and Enterotoxigenic Escherichia coli (ETEC) (7.15%) were the second and third most prevalent co-pathogens. Shigella (1.64%) was the second most common co-pathogen in the rural site. Azithromycin susceptibility increased slowly from 265 (8%) in 2006–2010 to 1485 (47.8%) in 2016–2021, and erythromycin susceptibility dropped substantially over 20 years period from 2,155 (98.4%) to 21 (0.9%). Tetracycline susceptibility decreased in the urban site from 2051 (45.9%) to 186 (4.2%) and ciprofloxacin susceptibility decreased from 2,581 (31.6%) to 1,360 (16.6%) until 2015, then increased 1,009 (22.6%) and 1,490 (18.2%) in 2016–2021, respectively. Since 2016, doxycycline showed 902 (100%) susceptibility. Clinicians need access to up-to-date information on antimicrobial susceptibility for treating hospitalized patients. To achieve the WHO-backed objective of eliminating cholera by 2030, the health systems need to be put under a proper surveillance system that may help to improve water and sanitation practices and deploy oral cholera vaccines strategically

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

BackgroundWorldwide, 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.ObjectivesThis 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.MethodsIn 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.ResultsA 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.ConclusionChildren 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

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 Enterotoxigenic Bacteroides fragilis Infection and Association with Environmental Enteric Dysfunction and Linear Growth in Children : Results from the MAL-ED Study

Despite reports of enterotoxigenic Bacteroides fragilis (ETBF) isolation from asymptomatic children, no reports exist regarding the possible association of ETBF with long-term complications such as development of environmental enteric dysfunction (EED) and subsequent linear growth faltering in childhood. We aimed to establish a potential association between the burden of asymptomatic ETBF infection and EED and linear growth at 24 months of age using the data collected from 1,715 children enrolled in the multi-country birth cohort study, known as the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health study. Using Poisson regression models, we evaluated the site-specific incidence rate and, subsequently, identified the risk factors and assessed the association between the burden of ETBF infection and EED score and linear growth at 24 months of age. The overall incidence rate of ETBF infections per 100 child-months across all study sites was 10.6%, with the highest and lowest incidence of ETBF infections being reported in Tanzania (19.6%) and Peru (3.6%), respectively. Female gender, longer duration of breastfeeding, and improved water access, sanitation, and hygiene practices, such as improved drinking water source, improved sanitation, and improved floor material in households, along with enhanced maternal education and less crowding in the households were found to be protective against incidences of ETBF infection. The burden of ETBF infections was found to have significant associations with EED and linear growth faltering at 24 months of age across all the study sites. Our findings warrant regular clinical monitoring to reduce the burden of ETBF infections and diminish the burden of enteropathy and linear growth faltering in childhood.publishedVersionPeer reviewe

Invasive Fungal Infections in Under-Five Diarrheal Children: Experience from an Urban Diarrheal Disease Hospital

Invasive fungal infections (IFIs) are opportunistic, especially in immunocompromised and hospitalized patients. Children with IFIs are more vulnerable to a fatal outcome. For early diagnosis and treatment, knowledge of the spectrum and frequency of IFIs among children is prerequisite. In this prospective observational study, we enrolled 168 children of 2–59 months old of either sex from March 2018 to December 2019 admitted to the Dhaka hospital, icddr,b. Study participants with suspected IFIs were with or without severe acute malnutrition (SAM) along with sepsis/pneumonia and fulfilled any of the following criteria: (i) failure to respond to injectable antibiotics, (ii) development of a late-onset hospital-acquired infection, (iii) needed ICU care for >7 days, (iv) took steroids/antibiotics for >2 weeks before hospitalization, and (v) developed thrush after taking injectable antibiotics. The comparison group included non-SAM (weight-for-length Z score ≥ −2) children with diarrhea and fever p = 0.013) and had a higher death rate (46.7% vs. 8.9%; p p = 0.042) after adjusting for potential confounders. Our findings thus implicate that, malnourished children with septic shock require targeted screening for the early diagnosis and prompt management of IFIs that may help to reduce IFIs related deaths

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 p 24 h history of diarrheal duration (p p 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

Exploratory Analysis of Selected Components of the mTOR Pathway Reveals Potentially Crucial Associations with Childhood Malnutrition

Dysregulations in the mammalian target of rapamycin (mTOR) pathway are associated with several human anomalies. We aimed to elucidate possible implications for potential aberrations in the mTOR pathway with childhood malnutrition. We analyzed the activity of phospho-mTORC1 and the expressions of several mTOR pathway genes, namely: MTOR, TSC1, LAMTOR2, RPS6K1 and RICTOR from peripheral blood mononuclear cells isolated from venous blood of children suffering from different forms of malnutrition and compared them with those from healthy children. Significant reduction in the phosphorylation of mTORC1 was noted, as well as a decrease in expression of LAMTOR2 gene and increase in TSC1 gene expression were observed between malnourished children in comparison to the healthy children. The deregulation in the activity of the TSC1 and LAMTOR2 gene was significantly associated with all forms of childhood malnutrition. Our findings provide key insights into possible down-modulation in the overall activity of the mTOR pathway in childhood malnutrition. Further studies focusing on the analysis of a multitude of components involved in the mTOR pathway both at the gene and protein expression levels are required for conclusive evidence for the aforementioned proposition.publishedVersionPeer reviewe

Effects of probiotic and synbiotic supplementation on ponderal and linear growth in severely malnourished young infants in a randomized clinical trial

Abstract Severe acute malnutrition (SAM) is a major global public health problem. We aimed to assess the effects of probiotic and synbiotic supplementation on rate of weight gain and change in length in young SAM infants. This study was substudy of a single-blind randomized clinical trial (NCT0366657). During nutritional rehabilitation, 67 <6 months old SAM infants were enrolled and randomized to receive either probiotic (Bifidobacterium. infantis EVC001) or synbiotic (B. infantis EVC001 + Lacto-N-neotetraose [LNnT]) or placebo (Lactose) for four weeks and were followed for four more weeks after supplementation. In multivariable linear regression model, the mean rate of weight gain in the probiotic arm compared to placebo was higher by 2.03 unit (P < 0.001), and 1.13 unit (P = 0.030) in the synbiotic arm. In linear mixed-effects model, mean WAZ was higher by 0.57 unit (P = 0.018) in probiotic arm compared to placebo. Although not statistically significant, delta length for age z score (LAZ) trended to be higher among children in probiotc (β = 0.25) and synbiotic (β = 0.26) arms compared to placebo in multivariable linear regression model. Our study describes that young SAM infants had a higher rate of weight gain when supplemented with probiotic alone, compared to their counterparts with either synbiotic or placebo

Association of human milk oligosaccharides and nutritional status of young infants among Bangladeshi mother-infant dyads.

Human milk oligosaccharides (HMOs) support the development of a healthy gut microbiome and the growth of infants. We aimed to determine the association of different HMOs with severe acute malnutrition (SAM) among Bangladeshi young infants. This study was nested within a single-blind, randomized, pilot clinical trial (NCT0366657). A total of 45 breastmilk samples from mothers of &lt; 6&nbsp;months old infants who had SAM (n = 26) or were non-malnourished (n = 19) and were analyzed for constituent HMOs. Of the infants with SAM, 14 (53.85%) had secretor mothers, and 11 (57.89%) of the non-malnourished infants had secretor mothers. A one-unit increase in the relative abundance of sialylated HMOs was associated with higher odds of SAM in age and sex adjusted model (aOR = 2.00, 90% CI 1.30, 3.06), in age, sex, and secretor status adjusted model (aOR = 1.96, 90% CI 1.29, 2.98), and also in age and sex adjusted model among non-secretor mothers (aOR = 2.86, 90% CI 1.07, 7.62). In adjusted models, there was no evidence of a statistically significant association between SAM and fucosylated or undecorated HMOs. Our study demonstrates that a higher relative abundance of sialylated HMOs in mothers' breastmilk may have a negative impact on young infants' nutritional status