Clinical, scientific and healthcare system consequences of misdiagnosing neonatal sepsis.

Introduction: Neonatal sepsis remains a major contributor to morbidity and mortality worldwide, with the highest burden in low- and middle-income countries (LMICs). Generating accurate estimates of disease burden is critical for setting research priorities, informing health policy, and resource allocation. However, in many LMICs, limited access to timely and reliable diagnostic tools severely limits case detection, undermines epidemiological surveillance, and impedes efforts to improve clinical outcomes.

Angiogenesis-associated pathways play critical roles in neonatal sepsis outcomes.

Neonatal sepsis is a major cause of childhood mortality. Limited diagnostic tools and mechanistic insights have hampered our abilities to develop prophylactic or therapeutic interventions. Biomarkers in human neonatal sepsis have been repeatedly identified as associated with dysregulation of angiopoietin signaling and altered arachidonic acid metabolism.

DDIT4L regulates mitochondrial and innate immune activities in early life.

Pattern recognition receptor responses are profoundly attenuated before the third trimester of gestation in the relatively low-oxygen human fetal environment. However, the mechanisms regulating these responses are uncharacterized. Herein, genome-wide transcription and functional metabolic experiments in primary neonatal monocytes linked the negative mTOR regulator DDIT4L to metabolic stress, cellular bioenergetics, and innate immune activity.

World Health Organization Danger Signs to predict bacterial sepsis in young infants: A pragmatic cohort study.

Bacterial sepsis is generally a major concern in ill infants. To help triaging decisions by front-line health workers in these situations, the World Health Organization (WHO) has developed danger signs (DS). The objective of this study was to evaluate the extent to which nine DS predict bacterial sepsis in young infants presenting with suspected sepsis in a low-income country setting.

Verbal Autopsy to Assess Postdischarge Mortality in Children With Suspected Sepsis in Uganda.

Background: Reducing child mortality in low-income countries is constrained by a lack of vital statistics. In the absence of such data, verbal autopsies provide an acceptable method to determining attributable causes of death. The objective was to assess potential causes of pediatric postdischarge mortality in children younger than age 5 years (under-5) originally admitted for suspected sepsis using verbal autopsies.

Whole blood genome-wide transcriptome profiling and metagenomics next-generation sequencing in young infants with suspected sepsis in a low-and middle-income country: A study protocol.

Conducting collaborative and comprehensive epidemiological research on neonatal sepsis in low- and middle-income countries (LMICs) is challenging due to a lack of diagnostic tests. This prospective study protocol aims to obtain epidemiological data on bacterial sepsis in newborns and young infants at Kamuzu Central Hospital in Lilongwe, Malawi. The main goal is to determine if the use of whole blood transcriptome host immune response signatures can help in the identification of infants who have sepsis of bacterial causes.

Neonatal sepsis in low-income countries: epidemiology, diagnosis and prevention.

: Sepsis accounts for up to one-third of neonatal deaths in the world each year. The World Health Organization acknowledges neonatal sepsis as a major global health concern, and that the highest burden occurs in low- and middle-income countries (LMICs). Despite major research and clinical progress in this area, we still lack accurate diagnostic tools for neonatal sepsis, complicating the management of this condition.

Outcomes related to respiratory syncytial virus with an abbreviated palivizumab regimen in children with congenital heart disease: a descriptive analysis.

Background: It has been hypothesized that 4 doses of palivizumab, a neutralizing monoclonal antibody against respiratory syncytial virus (RSV), administered during a fixed-date RSV season may reduce hospital admissions comparably to the standard 5-dose schedule. We report outcomes in children with congenital heart disease approved to receive this 4-dose palivizumab schedule in British Columbia.

Methods: We performed a population-based descriptive cohort analysis of all 406 approved palivizumab courses over 4 seasons (2012/13 to 2015/16) in 325 children with hemodynamically significant congenital heart disease enrolled in the British Columbia RSV Immunoprophylaxis Program.

Hyperoxia exposure impairs nephrogenesis in the neonatal rat: role of HIF-1α.

Preterm neonates are exposed at birth to high oxygen concentrations relative to the intrauterine environment. We have previously shown in a rat model that a hyperoxic insult results in a reduced nephron number in adulthood. Therefore, the aim of this study was to determine the effects of transient neonatal hyperoxia exposure on nephrogenesis.