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Article ; Online: Obstetric and Neonatal Invasive Meningococcal Disease Caused by Neisseria meningitidis Serogroup W, Western Australia, Australia.

Hart, Julie / Dowse, Gary K / Porter, Michelle / Speers, David J / Keil, Anthony D / Bew, Jane D / Mowlaboccus, Shakeel / Kahler, Charlene M

Emerging infectious diseases

2024 Volume 30, Issue 2, Page(s) 368–371

Abstract: Three mother-baby pairs with invasive meningococcal disease occurred over 7 months in Western Australia, Australia, at a time when serogroup W sequence type 11 clonal complex was the predominant local strain. One mother and 2 neonates died, highlighting ... ...

Abstract	Three mother-baby pairs with invasive meningococcal disease occurred over 7 months in Western Australia, Australia, at a time when serogroup W sequence type 11 clonal complex was the predominant local strain. One mother and 2 neonates died, highlighting the role of this strain as a cause of obstetric and early neonatal death.
MeSH term(s)	Humans ; Infant ; Infant, Newborn ; Female ; Pregnancy ; Western Australia/epidemiology ; Serogroup ; Australia/epidemiology ; Meningococcal Infections/epidemiology ; Neisseria meningitidis/genetics
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid3002.230639
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Article ; Online: Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial.

Rao, Shripada / Esvaran, Meera / Chen, Liwei / Keil, Anthony D / Gollow, Ian / Simmer, Karen / Wemheuer, Bernd / Conway, Patricia / Patole, Sanjay

Pediatric research

2022 Volume 92, Issue 4, Page(s) 1122–1131

Abstract: Objective: To evaluate whether probiotic supplementation attenuates gut-dysbiosis in neonates with congenital gastrointestinal surgical conditions (CGISC).: Methods: Sixty-one neonates (≥35 weeks gestation) with CGISC were randomised to receive daily ...

Abstract	Objective: To evaluate whether probiotic supplementation attenuates gut-dysbiosis in neonates with congenital gastrointestinal surgical conditions (CGISC). Methods: Sixty-one neonates (≥35 weeks gestation) with CGISC were randomised to receive daily supplementation with a triple-strain bifidobacterial probiotic (n = 30) or placebo (n = 31) until discharge. Stool microbiota was analysed using 16S ribosomal RNA gene sequencing on samples collected before (T1), 1 week (T2), and 2 weeks (T3) after supplementation and before discharge (T4). The primary outcome was the sum of the relative abundance of potentially pathogenic families of Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Pseudomonaceae, Staphylococcaeae, Streptococcaceae, and Yersiniaceae at T3. Results: The median gestational age [38 weeks (IQR: 37.1-38.9)] was similar in both groups. The probiotic group had lower rates of caesarean deliveries (40% versus 70%, p = 0.02). The relative abundance of potentially pathogenic families was lower in the probiotic group compared to placebo at T3 [(median: 50.4 (IQR: 26.6-67.6) versus 67.1 (IQR: 50.9-96.2); p = 0.04). Relative abundance of Bifidobacteriaceae was higher in the probiotic group at T3 [(median: 39.8 (IQR: 24.9-52.1) versus 0.03 (IQR 0.02-2.1); p < 0.001). Stratified analysis continued to show a higher abundance of Bifidobacteriaceae in the probiotic group, irrespective of the mode of delivery. Conclusions: Probiotic supplementation attenuated gut dysbiosis in neonates with CGISC. Trial registration: http://www.anzctr.org.au (ACTRN12617001401347). Impact: Probiotic supplementation attenuates gut dysbiosis and improves stool short-chain fatty acid levels in neonates with congenital gastrointestinal surgical conditions. This is the second pilot RCT of probiotic supplementation in neonates with congenital gastrointestinal conditions. These findings will pave the way for conducting multicentre RCTs in this area.
MeSH term(s)	Infant, Newborn ; Pregnancy ; Female ; Humans ; Infant ; Dysbiosis ; Pilot Projects ; Probiotics/therapeutic use ; Bifidobacterium ; Fatty Acids, Volatile ; Gastrointestinal Diseases
Chemical Substances	Fatty Acids, Volatile
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-021-01884-x
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Genomic dissection of the microevolution of Australian epidemic

Xu, Zheng / Hu, Dalong / Luu, Laurence Don Wai / Octavia, Sophie / Keil, Anthony D / Sintchenko, Vitali / Tanaka, Mark M / Mooi, Frits R / Robson, Jenny / Lan, Ruiting

Emerging microbes & infections

2022 Volume 11, Issue 1, Page(s) 1460–1473

Abstract: ... ...

Abstract	ABSTRACT
MeSH term(s)	Australia/epidemiology ; Bordetella pertussis ; Epidemics ; Genomics ; Humans ; Pertussis Vaccine ; Phylogeny ; Whooping Cough/epidemiology ; Whooping Cough/microbiology
Chemical Substances	Pertussis Vaccine
Language	English
Publishing date	2022-05-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2022.2077129
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Article ; Online: Sequencing of the Viral UL111a Gene Directly from Clinical Specimens Reveals Variants of HCMV-Encoded IL-10 That Are Associated with Altered Immune Responses to HCMV.

Waters, Shelley / Lee, Silvia / Ariyanto, Ibnu / Kresoje, Nina / Leary, Shay / Munyard, Kylie / Gaudieri, Silvana / Irish, Ashley / Keil, Anthony D / Allcock, Richard J N / Price, Patricia

International journal of molecular sciences

2022 Volume 23, Issue 9

Abstract: Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. Acute infections are often asymptomatic in healthy individuals but generate diverse syndromes in neonates, renal transplant recipients (RTR), and people with HIV (PWH) ...

Abstract	Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ~80% of adults worldwide. Acute infections are often asymptomatic in healthy individuals but generate diverse syndromes in neonates, renal transplant recipients (RTR), and people with HIV (PWH). The HCMV gene UL111a encodes a homolog of human interleukin-10 (IL-10) that interacts with the human IL-10 receptor. Deep sequencing technologies were used to sequence UL111a directly from 59 clinical samples from Indonesian PWH and Australian RTR, healthy adults, and neonates. Overall, 93% of samples contained more than one variant of HCMV, as defined by at least one nonsynonymous variation. Carriage of these variants differed between neonates and adults, Australians and Indonesians, and between saliva and blood leukocytes. The variant alleles of N41D and S71Y occurred together in Australian RTR and were associated with higher T-cell responses to HCMV pp65. The variant P122S was associated with lower levels of antibodies reactive with a lysate of HCMV-infected fibroblasts. L174F was associated with increased levels of antibodies reactive with HCMV lysate, immediate-early 1 (IE-1), and glycoprotein B (gB) in Australian RTR and Indonesians PWH, suggesting a higher viral burden. We conclude that variants of UL111a are common in all populations and may influence systemic responses to HCMV.
MeSH term(s)	Humans ; Australia ; Cytomegalovirus/genetics ; Cytomegalovirus Infections ; Immunity ; Indonesia ; Interleukin-10/genetics ; Viral Proteins/genetics
Chemical Substances	Interleukin-10 (130068-27-8) ; Viral Proteins ; UL111a protein, human cytomegalovirus
Language	English
Publishing date	2022-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23094644
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Article ; Online: Probiotic supplementation for neonates with congenital gastrointestinal surgical conditions: guidelines for future research.

Rao, Shripada / Esvaran, Meera / Chen, Liwei / Kok, Chooi / Keil, Anthony D / Gollow, Ian / Simmer, Karen / Wemheuer, Bernd / Conway, Patricia / Patole, Sanjay

Pediatric research

2022 Volume 93, Issue 1, Page(s) 49–55

Abstract: Our pilot RCT found that probiotic supplementation with the three-strain bifidobacterial product (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536) attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) ... ...

Abstract	Our pilot RCT found that probiotic supplementation with the three-strain bifidobacterial product (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536) attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions (CGISC). In this article, we have provided guidelines for designing future multicentre RCTs based on the experience gained from our pilot RCT. The recommendations include advice about sample size, potential confounders, outcomes of interest, probiotic strain selection, storage, dose, duration and microbial quality assurance, collection of stool samples, storage and analysis and reporting. Following these guidelines will increase the validity of future RCTs in this area and hence confidence in their results. IMPACT: Probiotic supplementation attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions. The current review provides evidence-based guidelines to conduct adequately powered RCTs in this field.
MeSH term(s)	Infant, Newborn ; Humans ; Dysbiosis ; Probiotics/therapeutic use ; Bifidobacterium ; Feces/microbiology ; Gastrointestinal Diseases
Language	English
Publishing date	2022-05-03
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	4411-8
ISSN	1530-0447 ; 0031-3998
ISSN (online)	1530-0447
ISSN	0031-3998
DOI	10.1038/s41390-022-02087-8
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Zs.A 564: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: RSV prophylaxis use in high-risk infants in Western Australia, 2002-2013: a record linkage cohort study.

Xu, Ruomei / Fathima, Parveen / Strunk, Tobias / de Klerk, Nicholas / Snelling, Thomas L / Richmond, Peter C / Keil, Anthony D / Moore, Hannah C

BMC pediatrics

2020 Volume 20, Issue 1, Page(s) 490

Abstract: Background: The monoclonal antibody, palivizumab is licensed for use in high-risk infants to prevent severe illness caused by respiratory syncytial virus (RSV). The level of its use and compliance with current jurisdictional guidelines which were ... ...

Abstract	Background: The monoclonal antibody, palivizumab is licensed for use in high-risk infants to prevent severe illness caused by respiratory syncytial virus (RSV). The level of its use and compliance with current jurisdictional guidelines which were amended in 2010, is unknown. We determined the level of palivizumab use in a cohort of high-risk infants in Western Australia. Methods: Using probabilistically linked administrative data, we conducted a birth cohort study within tertiary neonatal intensive care units (NICUs) born between 2002 and 2013. We described palivizumab use by patient characteristics, eligibility criteria according to guidelines over the period of study and identified predictors of its use. Results: Of 24,329 infants admitted to tertiary NICUs, 271 (1.1%) were dispensed 744 palivizumab doses with 62.5% being dispensed to infants born 2010-2013. The median number of doses received was 2. A total of 2679 infants met at least one of three criteria for palivizumab (criteria 1: gestational age at birth < 28 weeks and chronic lung disease; criteria 2: gestational age < 28 weeks and Aboriginal; criteria 3: congenital heart disease not otherwise in criteria 1 or 2). The extent of palivizumab use differed across the 3 groups. Of 803 infants meeting criteria 1, 21.8% received at least 1 dose of palivizumab; 52.8% from 2010 onwards. From 174 infants meeting criteria 2, 14.4% received at least 1 dose; 43.1% from 2010 onwards and from 1804 births meeting criteria 3, only 3.7% received at least 1 dose; 5.4% from year of birth 2010 onwards). In adjusted analyses, being born after 2010, being extreme preterm, chronic lung disease, congenital lung disease and being born in autumn or winter were independent predictors of palivizumab use. Conclusion: In this high-risk setting and notwithstanding the limitations of our data sources, the level of compliance of palivizumab use against current guidelines was low. Most doses were dispensed to infants meeting at least one high-risk criterion. Evidence of incomplete dosing is an important finding in light of recent developments of single dose monoclonal antibodies offering longer protection.
MeSH term(s)	Antibodies, Monoclonal, Humanized/therapeutic use ; Antiviral Agents/therapeutic use ; Cohort Studies ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Information Storage and Retrieval ; Palivizumab/therapeutic use ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/prevention & control ; Western Australia
Chemical Substances	Antibodies, Monoclonal, Humanized ; Antiviral Agents ; Palivizumab (DQ448MW7KS)
Language	English
Publishing date	2020-10-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041342-7
ISSN	1471-2431 ; 1471-2431
ISSN (online)	1471-2431
ISSN	1471-2431
DOI	10.1186/s12887-020-02390-5
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Article ; Online: Sequencing Directly from Clinical Specimens Reveals Genetic Variations in HCMV-Encoded Chemokine Receptor US28 That May Influence Antibody Levels and Interactions with Human Chemokines.

Waters, Shelley / Agostino, Mark / Lee, Silvia / Ariyanto, Ibnu / Kresoje, Nina / Leary, Shay / Munyard, Kylie / Gaudieri, Silvana / Gaff, Jessica / Irish, Ashley / Keil, Anthony D / Price, Patricia / Allcock, Richard J N

Microbiology spectrum

2021 Volume 9, Issue 2, Page(s) e0002021

Abstract: Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ∼80% of the world's population. Acute infections are asymptomatic in healthy individuals but generate diverse syndromes in neonates, solid organ transplant recipients, and HIV-infected ... ...

Abstract	Human cytomegalovirus (HCMV) is a beta-herpesvirus carried by ∼80% of the world's population. Acute infections are asymptomatic in healthy individuals but generate diverse syndromes in neonates, solid organ transplant recipients, and HIV-infected individuals. The HCMV gene US28 encodes a homolog of a human chemokine receptor that is able to bind several chemokines and HIV gp120. Deep sequencing technologies were used to sequence US28 directly from 60 clinical samples from Indonesian HIV patients and Australian renal transplant recipients, healthy adults, and neonates. Molecular modeling approaches were used to predict whether nine nonsynonymous mutations in US28 may alter protein binding to a panel of six chemokines and two variants of HIV gp120. Ninety-two percent of samples contained more than one variant of HCMV, as defined by at least one nonsynonymous mutation. Carriage of these variants differed between neonates and adults, Australian and Indonesian samples, and saliva samples and blood leukocytes. Two nonsynonymous mutations (N170D and R267K) were associated with increased levels of immediate early protein 1 (IE-1) and glycoprotein B (gB) HCMV-reactive antibodies, suggesting a higher viral burden. Seven of the nine mutations were predicted to alter binding of at least one ligand. Overall, HCMV variants are common in all populations and have the potential to affect US28 interactions with human chemokines and/or gp120 and alter responses to the virus. The findings relied on deep sequencing technologies applied directly to clinical samples, so the variants exist
MeSH term(s)	Adult ; Amino Acid Sequence/genetics ; Antibodies, Viral/blood ; Chemokines/metabolism ; Cytomegalovirus/genetics ; Cytomegalovirus/immunology ; Cytomegalovirus/isolation & purification ; Cytomegalovirus Infections/pathology ; Genetic Variation/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Mutation/genetics ; Protein Binding/genetics ; Receptors, Chemokine/genetics ; Receptors, Chemokine/immunology ; Signal Transduction ; Viral Proteins/genetics ; Viral Proteins/immunology ; Virus Attachment
Chemical Substances	Antibodies, Viral ; Chemokines ; Receptors, Chemokine ; US28 receptor, Cytomegalovirus ; Viral Proteins
Language	English
Publishing date	2021-10-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/Spectrum.00020-21
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Article ; Online: Effectiveness of Palivizumab against Respiratory Syncytial Virus: Cohort and Case Series Analysis.

Moore, Hannah C / de Klerk, Nicholas / Richmond, Peter C / Fathima, Parveen / Xu, Ruomei / Keil, Anthony D / Snelling, Thomas L / Strunk, Tobias

The Journal of pediatrics

2019 Volume 214, Page(s) 121–127.e1

Abstract: Objective: To measure the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants.: Study design: Palivizumab is funded for ...

Abstract	Objective: To measure the real-world effectiveness of palivizumab immunoprophylaxis against respiratory syncytial virus (RSV)-confirmed infection before age 2 years in a population-cohort of high-risk infants. Study design: Palivizumab is funded for high-risk infants in Western Australia. We used probabilistically linked administrative data encompassing RSV laboratory-confirmed infections, hospital admissions, and palivizumab dispensing records for a cohort of 24 329 high-risk infants admitted to neonatal intensive care units, born 2002-2013 with follow-up to 2015. We used a traditional cohort method with Cox proportional hazards regression and a self-controlled case series analysis to assess effectiveness of palivizumab in reducing RSV-confirmed infection by number of doses. Results: From the cohort of 24 329 infants, 271 (1.1%) received at least 1 dose of palivizumab and 1506 (6.2%) had at least 1 RSV-confirmed infection before age 2 years. Using the traditional cohort approach, we found no protective association of palivizumab receipt with RSV detection (adjusted hazard ratio = 0.99 [95% CI 0.5, 1.9] for 1 dose). However, using a self-controlled case series to eliminate confounding by indication, a protective association was seen with a 74% lower RSV incidence (relative incidence = 0.26; 95% CI 0.11, 0.67) following any dose of palivizumab compared with control (nonexposed) periods. Conclusions: After accounting for confounding by indication through a self-controlled analysis, palivizumab appeared effective for reducing virologically confirmed RSV in this high-risk cohort.
MeSH term(s)	Antiviral Agents/administration & dosage ; Child, Preschool ; DNA, Viral/analysis ; Dose-Response Relationship, Drug ; Female ; Follow-Up Studies ; Humans ; Incidence ; Infant ; Infant, Newborn ; Intensive Care Units, Neonatal/statistics & numerical data ; Male ; Palivizumab/administration & dosage ; Respiratory Syncytial Virus Infections/drug therapy ; Respiratory Syncytial Virus Infections/epidemiology ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Virus, Human/genetics ; Retrospective Studies ; Risk Factors ; Western Australia/epidemiology
Chemical Substances	Antiviral Agents ; DNA, Viral ; Palivizumab (DQ448MW7KS)
Language	English
Publishing date	2019-08-01
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2019.06.058
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Article ; Online: Developmental outcomes in cerebrospinal fluid proven enteroviral meningitis in neonates > 32 weeks of gestation.

Balasubramanian, Haribalakrishna / Wagh, Deepika / Rao, Shripada / Keil, Anthony D / McMichael, Judy

Journal of paediatrics and child health

2016 Volume 52, Issue 3, Page(s) 327–332

Abstract: Aim: The aim of this study is to assess the short-term and long-term (1 year) outcomes of cerebrospinal fluid (CSF) confirmed enteroviral meningitis in neonates > 32 weeks of gestation.: Methods: A retrospective audit of neonates admitted between 1 ... ...

Abstract	Aim: The aim of this study is to assess the short-term and long-term (1 year) outcomes of cerebrospinal fluid (CSF) confirmed enteroviral meningitis in neonates > 32 weeks of gestation. Methods: A retrospective audit of neonates admitted between 1 July 2002 to 30 June 2012. Results: Thirty-three neonates were diagnosed with enteroviral meningitis based on a positive CSF enteroviral PCR. Physical growth and neurodevelopmental outcomes at 1 year corrected for prematurity were available for 24 infants. All infants were alive at 1 year. The median weight, length and head circumference at 1 year were in the 72nd, 62nd and 78th centile and were comparable with the birth parameters. The mean general quotient (GQ) was 98.5 (SD 7.1) and was not significantly different from the population mean of 100.2 (P = 0.27). None of the infants had a GQ > 2SD below the population mean. Neurological recovery was complete in the 24 neonates assessed except one, who developed cerebral palsy, epilepsy and progressive hydrocephalus requiring ventriculoperitoneal shunt at 1 year. Conclusion: Neonatal enteroviral meningitis was associated with optimal growth and neurodevelopment in the majority of the infants at 1 year corrected for prematurity. Longer term studies are needed to better define developmental outcomes.
MeSH term(s)	Child Development/physiology ; Child, Preschool ; Cohort Studies ; Enterovirus Infections/cerebrospinal fluid ; Enterovirus Infections/diagnosis ; Enterovirus Infections/therapy ; Female ; Follow-Up Studies ; Gestational Age ; Growth/physiology ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Intensive Care Units, Neonatal ; Male ; Meningitis, Viral/diagnosis ; Meningitis, Viral/therapy ; Mental Health ; Pregnancy ; Reference Values ; Retrospective Studies ; Risk Assessment ; Severity of Illness Index
Language	English
Publishing date	2016-03
Publishing country	Australia
Document type	Journal Article
ZDB-ID	1024476-1
ISSN	1440-1754 ; 1034-4810
ISSN (online)	1440-1754
ISSN	1034-4810
DOI	10.1111/jpc.13083
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Article ; Online: Reply to Turnbull

Breuer, Oded / Schultz, Andre / Turkovic, Lidija / de Klerk, Nicholas / Keil, Anthony D / Brennan, Siobhain / Harrison, Joanne / Robertson, Colin / Robinson, Philip J / Sly, Peter D / Ranganathan, Sarath / Stick, Stephen M / Caudri, Daan

American journal of respiratory and critical care medicine

2020 Volume 201, Issue 6, Page(s) 750–752

MeSH term(s)	Child ; Child, Preschool ; Cystic Fibrosis ; Humans ; Infections ; Prevalence ; Respiratory System
Language	English
Publishing date	2020-01-09
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.201911-2213LE
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