Plasma proteomic signatures of enteric permeability among hospitalized and community children in Kenya and Pakistan

We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2: 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2: 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

Plasma proteomic signatures associated with enteric permeability among hospitalized and community children under two years of age in Kenya and Pakistan

We aimed to establish if enteric permeability was associated with similar biological processes in children recovering from hospitalization and relatively healthy children in the community. Extreme gradient boosted models predicting the lactulose-rhamnose ratio (LRR), a biomarker of enteric permeability, using 7,500 plasma proteins and 34 fecal biomarkers of enteric infection among 89 hospitalized and 60 community children aged 2–23 months were built. The R2 values were calculated in test sets. The models performed better among community children (R2 : 0.27 [min-max: 0.19, 0.53]) than hospitalized children (R2 : 0.07 [min-max: 0.03, 0.11]). In the community, LRR was associated with biomarkers of humoral antimicrobial and cellular lipopolysaccharide responses and inversely associated with anti-inflammatory and innate immunological responses. Among hospitalized children, the selected biomarkers had few shared functions. This suggests enteric permeability among community children was associated with a host response to pathogens, but this association was not observed among hospitalized children

Enteric permeability, systemic inflammation, and post-discharge growth among a cohort of hospitalized children in Kenya and Pakistan

Objectives: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. Methods: Children aged 2–23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. Results: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15–0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00–0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα (P = 0.017), CD14 (P = 0.078), and IL-6 (P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα (P = 0.004) and approached significance with CD14 (P = 0.078) and IL-6 (P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. Conclusions: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children

Clinical epidemiology of COVID-19 among hospitalized children in rural western Kenya

The epidemiology of pediatric COVID-19 in sub-Saharan Africa and the role of fecal-oral transmission in SARS-CoV-2 are poorly understood. Among children and adolescents in Kenya, we identify correlates of COVID-19 infection, document the clinical outcomes of infection, and evaluate the prevalence and viability of SARS-CoV-2 in stool. We recruited a prospective cohort of hospitalized children aged two months to 15 years in western Kenya between March 1 and June 30 2021. Children with SARS-CoV-2 were followed monthly for 180-days after hospital discharge. Bivariable logistic regression analysis was used to identify the clinical and sociodemographics correlates of SARS-CoV-2 infection. We also calculated the prevalence of SARS-CoV-2 detection in stool of confirmed cases. Of 355 systematically tested children, 55 (15.5%) were positive and were included in the cohort. The commonest clinical features among COVID-19 cases were fever (42/55, 76%), cough (19/55, 35%), nausea and vomiting (19/55, 35%), and lethargy (19/55, 35%). There were no statistically significant difference in baseline sociodemographic and clinical characteristics between SARS-CoV-2 positive and negative participants. Among positive participants, 8/55 (14.5%, 95%CI: 5.3%-23.9%) died; seven during the inpatient period. Forty-nine children with COVID-19 had stool samples or rectal swabs available at baseline, 9 (17%) had PCR-positive stool or rectal swabs, but none had SARS-CoV-2 detected by culture. Syndromic identification of COVID-19 is particularly challenging among children as the presenting symptoms and signs mirror other common pediatric diseases. Mortality among children hospitalized with COVID-19 was high in this cohort but was comparable to mortality seen with other common illnesses in this setting. Among this small set of children with COVID-19 we detected SARS-CoV-2 DNA, but were not able to culture viable SARs-CoV-2 virus, in stool. This suggests that fecal transmission may not be a substantial risk in children recently diagnosed and hospitalized with COVID-19 infection

Enteric Permeability, Systemic Inflammation, and Post-Discharge Growth among a Cohort of Hospitalized Children in Kenya and Pakistan

Funding Information: Sources of Funding: The CHAIN Network is supported by the Bill & Melinda Gates Foundation [OPP1131320]. For the purpose of Open Access, the authors have applied a CC-BY public copyright license to any author accepted manuscript version arising from this submission. The lactulose-rhamnose testing was funded by an Early Career Award from the Thrasher Research Foundation. The funders had no role in conduct of the study, interpretation, writing the manuscript or decision to submit. No authors were paid to write this article by any company, organization or agency. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.Objectives: To determine whether gut permeability is associated with post-discharge growth and systemic inflammation among hospitalized children in low- and middle-income countries. Methods: Children aged 2-23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose-rhamnose ratio (LRR) permeability testing and were compared to age-matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length-for-age (LAZ) and weight-for-age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation [C-reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin-6 (IL-6)], and enterocyte damage [Intestinal Fatty-Acid Binding protein (I-FABP)] differed between the hospitalized and community groups. Results: One hundred thirty-seven hospitalized and 84 community participants were included. The hospitalized group had higher log-LRR [0.43, 95% confidence interval (CI): 0.15-0.71, P = 0.003] than the community children. Adjustment for weight-for-length z score at discharge attenuated this association (0.31, 95% CI: 0.00-0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post-discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα (P = 0.017), CD14 (P = 0.078), and IL-6 (P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα (P = 0.004) and approached significance with CD14 (P = 0.078) and IL-6 (P = 0.062) in community children, but there was no evidence of these associations among hospitalized children. Conclusions: Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post-discharge growth among hospitalized children.Peer reviewe

Data Management in Multicountry Consortium Studies: The Enterics For Global Health (EFGH) Shigella Surveillance Study Example

Background: Rigorous data management systems and planning are essential to successful research projects, especially for large, multicountry consortium studies involving partnerships across multiple institutions. Here we describe the development and implementation of data management systems and procedures for the Enterics For Global Health (EFGH) Shigella surveillance study—a 7-country diarrhea surveillance study that will conduct facility-based surveillance concurrent with population-based enumeration and a health care utilization survey to estimate the incidence of Shigella­-associated diarrhea in children 6 to 35 months old. Methods: The goals of EFGH data management are to utilize the knowledge and experience of consortium members to collect high-quality data and ensure equity in access and decision-making. During the planning phase before study initiation, a working group of representatives from each EFGH country site, the coordination team, and other partners met regularly to develop the data management systems for the study. Results: This resulted in the Data Management Plan, which included selecting REDCap and SurveyCTO as the primary database systems. Consequently, we laid out procedures for data processing and storage, study monitoring and reporting, data quality control and assurance activities, and data access. The data management system and associated real-time visualizations allow for rapid data cleaning activities and progress monitoring and will enable quicker time to analysis. Conclusions: Experiences from this study will contribute toward enriching the sparse landscape of data management methods publications and serve as a case study for future studies seeking to collect and manage data consistently and rigorously while maintaining equitable access to and control of data

Boronic acids for sensing and other applications - a mini-review of papers published in 2013

Boronic acids are increasingly utilised in diverse areas of research. Including the interactions of boronic acids with diols and strong Lewis bases as fluoride or cyanide anions, which leads to their utility in various sensing applications. The sensing applications can be homogeneous assays or heterogeneous detection. Detection can be at the interface of the sensing material or within the bulk sample. Furthermore, the key interaction of boronic acids with diols allows utilisation in various areas ranging from biological labelling, protein manipulation and modification, separation and the development of therapeutics. All the above uses and applications are covered by this mini-review of papers published during 2013