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Article ; Online: Look Who’s Talking

Isabella A. Joubert / Michael Otto / Tobias Strunk / Andrew J. Currie

International Journal of Molecular Sciences, Vol 23, Iss 860, p

Host and Pathogen Drivers of Staphylococcus epidermidis Virulence in Neonatal Sepsis

2022 Volume 860

Abstract: Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis , a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants ... ...

Abstract	Preterm infants are at increased risk for invasive neonatal bacterial infections. S. epidermidis , a ubiquitous skin commensal, is a major cause of late-onset neonatal sepsis, particularly in high-resource settings. The vulnerability of preterm infants to serious bacterial infections is commonly attributed to their distinct and developing immune system. While developmentally immature immune defences play a large role in facilitating bacterial invasion, this fails to explain why only a subset of infants develop infections with low-virulence organisms when exposed to similar risk factors in the neonatal ICU. Experimental research has explored potential virulence mechanisms contributing to the pathogenic shift of commensal S. epidermidis strains. Furthermore, comparative genomics studies have yielded insights into the emergence and spread of nosocomial S. epidermidis strains, and their genetic and functional characteristics implicated in invasive disease in neonates. These studies have highlighted the multifactorial nature of S. epidermidis traits relating to pathogenicity and commensalism. In this review, we discuss the known host and pathogen drivers of S. epidermidis virulence in neonatal sepsis and provide future perspectives to close the gap in our understanding of S. epidermidis as a cause of neonatal morbidity and mortality.
Keywords	host–pathogen interactions ; neonatal sepsis ; S. epidermidis ; commensalism ; pathogenesis ; virulence ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Composition of early life leukocyte populations in preterm infants with and without late-onset sepsis.

Julie Hibbert / Tobias Strunk / Elizabeth Nathan / Amy Prosser / Dorota Doherty / Karen Simmer / Peter Richmond / David Burgner / Andrew Currie

PLoS ONE, Vol 17, Iss 3, p e

2022 Volume 0264768

Abstract: Background Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim To characterise and compare leukocyte populations in preterm ... ...

Abstract	Background Composition of leukocyte populations in the first month of life remains incompletely characterised, particularly in preterm infants who go on to develop late-onset sepsis (LOS). Aim To characterise and compare leukocyte populations in preterm infants with and without LOS during the first month of life. Study design Single-centre prospective observational cohort study. Participants Infants born <30 weeks gestational age (GA). Outcome measures Peripheral blood samples were collected at 1, 7, 14, 21 and 28 days of life. Leukocyte populations were characterised using 5-fluorophore-6-marker flow cytometry. Absolute leukocyte counts and frequency of total CD45+ leukocytes of each population were adjusted for GA, birth weight z-scores, sex and total leukocyte count. Results Of 119 preterm infants enrolled, 43 (36%) had confirmed or clinical LOS, with a median onset at 13 days (range 6-26). Compared to infants without LOS, the adjusted counts and frequency of neutrophils, basophils and non-cytotoxic T lymphocytes were generally lower and immature granulocytes were higher over the first month of life in infants who developed LOS. Specific time point comparisons identified lower adjusted neutrophil counts on the first day of life in those infants who developed LOS more than a week later, compared to those without LOS, albeit levels were within the normal age-adjusted range. Non-cytotoxic T lymphocyte counts and/or frequencies were lower in infants following LOS on days 21 and 28 when compared to those who did not develop LOS. Conclusion Changes in non-cytotoxic T lymphocytes occurred following LOS suggesting sepsis-induced immune suppression.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Plasma cytokine profiles in very preterm infants with late-onset sepsis.

Julie Hibbert / Tobias Strunk / Karen Simmer / Peter Richmond / David Burgner / Andrew Currie

PLoS ONE, Vol 15, Iss 5, p e

2020 Volume 0232933

Abstract: INTRODUCTION:Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood. AIMS:To characterise ... ...

Abstract	INTRODUCTION:Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood. AIMS:To characterise plasma pro- and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS). METHODS:In this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay. RESULTS:IL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1β, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without. CONCLUSION:Very preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Skin-Microbiome Assembly in Preterm Infants during the First Three Weeks of Life and Impact of Topical Coconut Oil Application

Noor-Ul-Huda Ghori / Christopher A. Mullally / Mark P. Nicol / Andrew Currie / Julie Hibbert / Matthew S. Payne / Sanjay Patole / Tobias Strunk

International Journal of Molecular Sciences, Vol 24, Iss 23, p

2023 Volume 16626

Abstract: The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, ... ...

Abstract	The structure and function of infant skin is not fully developed until 34 weeks of gestation, and this immaturity is associated with risk of late-onset sepsis (LOS). Topical coconut oil improves preterm-infant skin integrity and may reduce LOS. However, data on early-life skin-microbiome succession and potential effects of emollient skin care in preterm infants are scarce. We therefore collected skin-microbiome samples from the ear, axilla, and groin on days 1, 7, 14, and 21 from preterm infants born <30 weeks of gestation as part of a randomized clinical trial of standard skin care vs. topical coconut oil. We found that within-sample microbiome diversity was highest on day 1 after birth, with a subsequent decline and emergence of Staphylococcus genus dominance from day 7. Moreover, microbiome assembly was less diverse in infants receiving coconut oil vs. standard skin care. Our study provides novel data on preterm-infant skin-microbiome composition and highlights the modifying potential of emollient skin care.
Keywords	coconut oil ; preterm infants ; skin microbiome ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 571
Language	English
Publishing date	2023-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Precision Medicine for Neonatal Sepsis

Sherrianne Ng / Tobias Strunk / Pingping Jiang / Tik Muk / Per T. Sangild / Andrew Currie

Frontiers in Molecular Biosciences, Vol

2018 Volume 5

Abstract: Neonatal sepsis remains a significant cause of morbidity and mortality especially in the preterm infant population. The ability to promptly and accurately diagnose neonatal sepsis based on clinical evaluation and laboratory blood tests remains ... ...

Abstract	Neonatal sepsis remains a significant cause of morbidity and mortality especially in the preterm infant population. The ability to promptly and accurately diagnose neonatal sepsis based on clinical evaluation and laboratory blood tests remains challenging. Advances in high-throughput molecular technologies have increased investigations into the utility of transcriptomic, proteomic and metabolomic approaches as diagnostic tools for neonatal sepsis. A systems-level understanding of neonatal sepsis, obtained by using omics-based technologies (at the transcriptome, proteome or metabolome level), may lead to new diagnostic tools for neonatal sepsis. In particular, recent omic-based studies have identified distinct transcriptional signatures and metabolic or proteomic biomarkers associated with sepsis. Despite the emerging need for a systems biology approach, future studies have to address the challenges of integrating multi-omic data with laboratory and clinical meta-data in order to translate outcomes into precision medicine for neonatal sepsis. Omics-based analytical approaches may advance diagnostic tools for neonatal sepsis. More research is needed to validate the recent systems biology findings in order to integrate multi-dimensional data (clinical, laboratory and multi-omic) for future translation into precision medicine for neonatal sepsis. This review will discuss the possible applications of omics-based analyses for identification of new biomarkers and diagnostic signatures for neonatal sepsis, focusing on the immune-compromised preterm infant and considerations for clinical translation.
Keywords	systems biology ; diagnosis ; infection ; neonate ; sepsis ; preterm infant ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2018-07-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Effects of lactoferrin on neonatal pathogens and Bifidobacterium breve in human breast milk.

Tabitha Woodman / Tobias Strunk / Sanjay Patole / Benjamin Hartmann / Karen Simmer / Andrew Currie

PLoS ONE, Vol 13, Iss 8, p e

2018 Volume 0201819

Abstract: Supplementation with probiotics in preterm infants reduces necrotizing enterocolitis and sepsis. Bovine lactoferrin is a promising supplement that may further reduce disease burden, but its effects on probiotic bacteria in human breast milk has not been ... ...

Abstract	Supplementation with probiotics in preterm infants reduces necrotizing enterocolitis and sepsis. Bovine lactoferrin is a promising supplement that may further reduce disease burden, but its effects on probiotic bacteria in human breast milk has not been evaluated. We aimed to characterise the antimicrobial activity of bovine and human lactoferrin in human breast milk against probiotics and typical neonatal sepsis pathogens. Lactoferrin levels were determined by enzyme linked immunosorbent assay in fresh and pasteurised human breast milk. The neonatal pathogens Staphylococcus epidermidis and Escherichia coli, and the probiotic Bifidobacterium breve strain M-16V were cultured in human breast milk or infant formula in the presence or absence of clinically relevant doses of bovine or human lactoferrin. Standard microbiological methods were used to determine the effects of lactoferrin on bacterial growth. Unpasteurised human breast milk contained significantly higher lactoferrin levels and resulted in superior inhibition of pathogenic bacterial growth compared to infant formula and pasteurised human breast milk. Human lactoferrin was significantly more effective at inhibiting bacterial growth, when compared to bovine lactoferrin. Supplementation with human lactoferrin or high dose bovine lactoferrin inhibited growth of the probiotic strain B. breve M-16V in pasteurised human breast milk. Although unpasteurised human breast milk and human lactoferrin had the greatest antimicrobial activity against all bacterial species tested, higher doses of bovine lactoferrin also showed activity against B. breve and. S. epidermidis. This study suggests that simultaneous administration of lactoferrins and probiotics may affect colonisation with probiotic bacteria, warranting further investigations.
Keywords	Medicine ; R ; Science ; Q
Subject code	616 ; 610
Language	English
Publishing date	2018-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protocol for the development of a core outcome set for neonatal sepsis (NESCOS)

Petek Eylul Taneri / Jamie J. Kirkham / Eleanor J. Molloy / Linda Biesty / Richard A. Polin / James L. Wynn / Barbara J. Stoll / Niranjan Kissoon / Kondwani Kawaza / Mandy Daly / Aoife Branagan / Lívia Nagy Bonnard / Eric Giannoni / Tobias Strunk / Magdalena Ohaja / Kenneth Mugabe / Denise Suguitani / Fiona Quirke / Declan Devane

PLoS ONE, Vol 18, Iss

2023 Volume 12

Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protocol for the development of a core outcome set for neonatal sepsis (NESCOS).

Petek Eylul Taneri / Jamie J Kirkham / Eleanor J Molloy / Linda Biesty / Richard A Polin / James L Wynn / Barbara J Stoll / Niranjan Kissoon / Kondwani Kawaza / Mandy Daly / Aoife Branagan / Lívia Nagy Bonnard / Eric Giannoni / Tobias Strunk / Magdalena Ohaja / Kenneth Mugabe / Denise Suguitani / Fiona Quirke / Declan Devane

PLoS ONE, Vol 18, Iss 12, p e

2023 Volume 0295325

Abstract: Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for ... ...

Abstract	Neonatal sepsis is a serious public health problem; however, there is substantial heterogeneity in the outcomes measured and reported in research evaluating the effectiveness of the treatments. Therefore, we aim to develop a Core Outcome Set (COS) for studies evaluating the effectiveness of treatments for neonatal sepsis. Since a systematic review of key outcomes from randomised trials of therapeutic interventions in neonatal sepsis was published recently, we will complement this with a qualitative systematic review of the key outcomes of neonatal sepsis identified by parents, other family members, parent representatives, healthcare providers, policymakers, and researchers. We will interpret the outcomes of both studies using a previously established framework. Stakeholders across three different groups i.e., (1) researchers, (2) healthcare providers, and (3) patients' parents/family members and parent representatives will rate the importance of the outcomes in an online Real-Time Delphi Survey. Afterwards, consensus meetings will be held to agree on the final COS through online discussions with key stakeholders. This COS is expected to minimize outcome heterogeneity in measurements and publications, improve comparability and synthesis, and decrease research waste.
Keywords	Medicine ; R ; Science ; Q
Subject code	306
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Whole blood transcriptional responses of very preterm infants during late-onset sepsis.

Sherrianne Ng / Tobias Strunk / Amy H Lee / Erin E Gill / Reza Falsafi / Tabitha Woodman / Julie Hibbert / Robert E W Hancock / Andrew Currie

PLoS ONE, Vol 15, Iss 6, p e

2020 Volume 0233841

Abstract: BACKGROUND:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased ... ...

Abstract	BACKGROUND:Host immune responses during late-onset sepsis (LOS) in very preterm infants are poorly characterised due to a complex and dynamic pathophysiology and challenges in working with small available blood volumes. We present here an unbiased transcriptomic analysis of whole peripheral blood from very preterm infants at the time of LOS. METHODS:RNA-Seq was performed on peripheral blood samples (6-29 days postnatal age) taken at the time of suspected LOS from very preterm infants <30 weeks gestational age. Infants were classified based on blood culture positivity and elevated C-reactive protein concentrations as having confirmed LOS (n = 5), possible LOS (n = 4) or no LOS (n = 9). Bioinformatics and statistical analyses performed included pathway over-representation and protein-protein interaction network analyses. Plasma cytokine immunoassays were performed to validate differentially expressed cytokine pathways. RESULTS:The blood leukocyte transcriptional responses of infants with confirmed LOS differed significantly from infants without LOS (1,317 differentially expressed genes). However, infants with possible LOS could not be distinguished from infants with no LOS or confirmed LOS. Transcriptional alterations associated with LOS included genes involved in pathogen recognition (mainly TLR pathways), cytokine signalling (both pro-inflammatory and inhibitory responses), immune and haematological regulation (including cell death pathways), and metabolism (altered cholesterol biosynthesis). At the transcriptional-level cytokine responses during LOS were characterised by over-representation of IFN-α/β, IFN-γ, IL-1 and IL-6 signalling pathways and up-regulation of genes for inflammatory responses. Infants with confirmed LOS had significantly higher levels of IL-1α and IL-6 in their plasma. CONCLUSIONS:Blood responses in very preterm infants with LOS are characterised by altered host immune responses that appear to reflect unbalanced immuno-metabolic homeostasis.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mode of birth and risk of infection-related hospitalisation in childhood

Jessica E Miller / Raphael Goldacre / Hannah C Moore / Justin Zeltzer / Marian Knight / Carole Morris / Sian Nowell / Rachael Wood / Kim W Carter / Parveen Fathima / Nicholas de Klerk / Tobias Strunk / Jiong Li / Natasha Nassar / Lars H Pedersen / David P Burgner

PLoS Medicine, Vol 17, Iss 11, p e

A population cohort study of 7.17 million births from 4 high-income countries.

2020 Volume 1003429

Abstract: Background The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated ... ...

Abstract	Background The proportion of births via cesarean section (CS) varies worldwide and in many countries exceeds WHO-recommended rates. Long-term health outcomes for children born by CS are poorly understood, but limited data suggest that CS is associated with increased infection-related hospitalisation. We investigated the relationship between mode of birth and childhood infection-related hospitalisation in high-income countries with varying CS rates. Methods and findings We conducted a multicountry population-based cohort study of all recorded singleton live births from January 1, 1996 to December 31, 2015 using record-linked birth and hospitalisation data from Denmark, Scotland, England, and Australia (New South Wales and Western Australia). Birth years within the date range varied by site, but data were available from at least 2001 to 2010 for each site. Mode of birth was categorised as vaginal or CS (emergency/elective). Infection-related hospitalisations (overall and by clinical type) occurring after the birth-related discharge date were identified in children until 5 years of age by primary/secondary International Classification of Diseases, 10th Revision (ICD-10) diagnosis codes. Analysis used Cox regression models, adjusting for maternal factors, birth parameters, and socioeconomic status, with results pooled using meta-analysis. In total, 7,174,787 live recorded births were included. Of these, 1,681,966 (23%, range by jurisdiction 17%-29%) were by CS, of which 727,755 (43%, range 38%-57%) were elective. A total of 1,502,537 offspring (21%) had at least 1 infection-related hospitalisation. Compared to vaginally born children, risk of infection was greater among CS-born children (hazard ratio (HR) from random effects model, HR 1.10, 95% confidence interval (CI) 1.09-1.12, p < 0.001). The risk was higher following both elective (HR 1.13, 95% CI 1.12-1.13, p < 0.001) and emergency CS (HR 1.09, 95% CI 1.06-1.12, p < 0.001). Increased risks persisted to 5 years and were highest for respiratory, ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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