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1.
Emerg Infect Dis ; 30(2): 368-371, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38270157

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.


Subject(s)
Meningococcal Infections , Neisseria meningitidis , Humans , Infant , Infant, Newborn , Female , Pregnancy , Western Australia/epidemiology , Serogroup , Australia/epidemiology , Meningococcal Infections/epidemiology , Neisseria meningitidis/genetics
2.
Pediatr Res ; 93(1): 49-55, 2023 01.
Article in English | MEDLINE | ID: mdl-35505080

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.


Subject(s)
Gastrointestinal Diseases , Probiotics , Infant, Newborn , Humans , Dysbiosis , Probiotics/therapeutic use , Bifidobacterium , Feces/microbiology
3.
Int J Mol Sci ; 23(9)2022 Apr 22.
Article in English | MEDLINE | ID: mdl-35563032

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.


Subject(s)
Cytomegalovirus Infections , Cytomegalovirus , Interleukin-10 , Viral Proteins , Humans , Australia , Cytomegalovirus/genetics , Immunity , Indonesia , Interleukin-10/genetics , Viral Proteins/genetics
4.
Emerg Microbes Infect ; 11(1): 1460-1473, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35543519

ABSTRACT

ABSTRACTWhooping cough (pertussis) is a highly contagious respiratory disease caused by the bacterium Bordetella pertussis. Despite high vaccine coverage, pertussis has re-emerged in many countries including Australia and caused two large epidemics in Australia since 2007. Here, we undertook a genomic and phylogeographic study of 385 Australian B. pertussis isolates collected from 2008 to 2017. The Australian B. pertussis population was found to be composed of mostly ptxP3 strains carrying different fim3 alleles, with ptxP3-fim3A genotype expanding far more than ptxP3-fim3B. Within the former, there were six co-circulating epidemic lineages (EL1 to EL6). The multiple ELs emerged, expanded, and then declined at different time points over the two epidemics. In population genetics terms, both hard and soft selective sweeps through vaccine selection pressures have determined the population dynamics of Australian B. pertussis. Relative risk estimation suggests that once a new B. pertussis lineage emerged, it was more likely to spread locally within the first 1.5 years. However, after 1.5 years, any new lineage was likely to expand to a wider region. Phylogenetic analysis revealed the expansion of ptxP3 strains was also associated with replacement of the type III secretion system allele bscI1 with bscI3. bscI3 is associated with decreased T3SS secretion and may allow B. pertussis to reduce immune recognition. This study advanced our understanding of the epidemic population structure and spatial and temporal dynamics of B. pertussis in a highly immunized population.


Subject(s)
Epidemics , Whooping Cough , Australia/epidemiology , Bordetella pertussis , Genomics , Humans , Pertussis Vaccine , Phylogeny , Whooping Cough/epidemiology , Whooping Cough/microbiology
5.
Eur J Pediatr ; 181(6): 2249-2262, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35348825

ABSTRACT

Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks' gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment. CONCLUSION: Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised. WHAT IS KNOWN: • Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants. • Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants. WHAT IS NEW: • This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants. • All except one case where the diagnosis was uncertain recovered after antimicrobial therapy.


Subject(s)
Enterocolitis, Necrotizing , Probiotics , Sepsis , Anti-Bacterial Agents , Antifungal Agents , Enterocolitis, Necrotizing/epidemiology , Humans , Infant , Infant, Newborn , Infant, Premature , Probiotics/therapeutic use , Randomized Controlled Trials as Topic , Sepsis/etiology , Sepsis/prevention & control
6.
Article in English | MEDLINE | ID: mdl-35185013

ABSTRACT

OBJECTIVE: Evidence indicates that multistrain probiotics benefit preterm infants more than single-strain (SS) probiotics. We assessed the effects of SS versus triple-strain (TS) probiotic supplementation (PS) in extremely preterm (EP) infants. DESIGN: EP infants (gestational age (GA) <28 weeks) were randomly allocated to TS or SS probiotic, assuring blinding. Reference (REF) group was EP infants in the placebo arm of our previous probiotic trial. PS was commenced with feeds and continued until 37 weeks' corrected GA. Primary outcome was time to full feed (TFF: 150 mL/kg/day). Secondary outcomes included short-chain fatty acids and faecal microbiota collected at T1 (first week) and T2 (after 3 weeks of PS) using 16S ribosomal RNA gene sequencing. RESULTS: 173 EP (SS: 86, TS: 87) neonates with similar GA and birth weight (BW) were randomised. Median TFF was comparable (11 (IQR 8-16) vs 10 (IQR 8-16) days, p=0.92). Faecal propionate (SS, p<0.001, and TS, p=0.0009) and butyrate levels (TS, p=0.029) were significantly raised in T2 versus T1 samples. Secondary clinical outcomes were comparable. At T2, alpha diversity was comparable (p>0.05) between groups, whereas beta-diversity analysis revealed significant differences between PS and REF groups (both p=0.001). Actinobacteria were higher (both p<0.01), and Proteobacteria, Firmicutes and Bacteroidetes were lower in PS versus REF. Gammaproteobacteria, Clostridia and Negativicutes were lower in both PS versus REF. CONCLUSION: TFF in EP infants was similar between SS and TS probiotics. Both probiotics were effective in reducing dysbiosis (higher bifidobacteria and lower Gammaproteobacteria). Long-term significance of increased propionate and butyrate needs further studies. TRIAL REGISTRATION NUMBER: ACTRN 12615000940572.


Subject(s)
Infant, Extremely Premature , Probiotics , Bifidobacterium , Butyrates , Firmicutes , Humans , Infant , Infant, Newborn , Probiotics/therapeutic use , Propionates
7.
Pediatr Res ; 92(4): 1122-1131, 2022 10.
Article in English | MEDLINE | ID: mdl-34980887

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.


Subject(s)
Gastrointestinal Diseases , Probiotics , Infant, Newborn , Pregnancy , Female , Humans , Infant , Dysbiosis , Pilot Projects , Probiotics/therapeutic use , Bifidobacterium , Fatty Acids, Volatile
8.
Microbiol Spectr ; 9(2): e0002021, 2021 10 31.
Article in English | MEDLINE | ID: mdl-34704798

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 in vivo. IMPORTANCE Human cytomegalovirus (HCMV) is a common viral pathogen of solid organ transplant recipients, neonates, and HIV-infected individuals. HCMV encodes homologs of several host genes with the potential to influence viral persistence and/or pathogenesis. Here, we present deep sequencing of an HCMV chemokine receptor homolog, US28, acquired directly from clinical specimens. Carriage of these variants differed between patient groups and was associated with different levels of circulating HCMV-reactive antibodies. These features are consistent with a role for US28 in HCMV persistence and pathogenesis. This was supported by in silico analyses of the variant sequences demonstrating altered ligand-binding profiles. The data delineate a novel approach to understanding the pathogenesis of HCMV and may impact the development of an effective vaccine.


Subject(s)
Antibodies, Viral/blood , Chemokines/metabolism , Cytomegalovirus/genetics , Cytomegalovirus/immunology , Receptors, Chemokine/genetics , Viral Proteins/genetics , Virus Attachment , Adult , Amino Acid Sequence/genetics , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/pathology , Genetic Variation/genetics , High-Throughput Nucleotide Sequencing , Humans , Infant , Infant, Newborn , Mutation/genetics , Protein Binding/genetics , Receptors, Chemokine/immunology , Signal Transduction , Viral Proteins/immunology
9.
Burns ; 47(3): 569-575, 2021 05.
Article in English | MEDLINE | ID: mdl-33858714

ABSTRACT

AIM: To evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit. BACKGROUND: Burn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them. METHODS: An interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice. RESULTS: During the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013. CONCLUSION: The implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.


Subject(s)
Burns/complications , Infection Control/instrumentation , Adolescent , Burn Units/organization & administration , Burn Units/statistics & numerical data , Burns/epidemiology , Burns/therapy , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Infection Control/methods , Infection Control/statistics & numerical data , Interrupted Time Series Analysis/methods , Male , Prospective Studies , Retrospective Studies , Western Australia/epidemiology , Wound Infection/epidemiology , Wound Infection/etiology , Wound Infection/physiopathology
10.
BMC Pediatr ; 20(1): 490, 2020 10 22.
Article in English | MEDLINE | ID: mdl-33092566

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.


Subject(s)
Respiratory Syncytial Virus Infections , 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
11.
Pediatr Res ; 88(6): 878-886, 2020 12.
Article in English | MEDLINE | ID: mdl-32179871

ABSTRACT

BACKGROUND: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available. METHODS: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10-14 days of life (week 2). RESULTS: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia-Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001). CONCLUSIONS: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs. IMPACT: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.


Subject(s)
Gastrointestinal Diseases/complications , Gastrointestinal Microbiome , Bacteroides , Bifidobacterium , Calibration , Escherichia coli , Fatty Acids, Volatile/metabolism , Feces/microbiology , Female , Gas Chromatography-Mass Spectrometry , Gastrointestinal Diseases/congenital , Hospitalization , Humans , Infant, Extremely Premature , Infant, Newborn , Infant, Premature , Linear Models , Male , Polymerase Chain Reaction , Prospective Studies , Pseudomonas , RNA, Ribosomal, 16S , Risk Factors , Shigella , Treatment Outcome
13.
J Pediatr ; 214: 121-127.e1, 2019 11.
Article in English | MEDLINE | ID: mdl-31378522

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.


Subject(s)
Palivizumab/administration & dosage , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus, Human/genetics , 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 , Respiratory Syncytial Virus Infections/epidemiology , Respiratory Syncytial Virus Infections/virology , Retrospective Studies , Risk Factors , Western Australia/epidemiology
15.
Am J Respir Crit Care Med ; 200(5): 590-599, 2019 09 01.
Article in English | MEDLINE | ID: mdl-30811949

ABSTRACT

Rationale: Historical studies suggest that airway infection in cystic fibrosis initiates with Staphylococcus aureus and Haemophilus influenzae, with later emergence of Pseudomonas aeruginosa. Aspergillus species are regarded as relatively infrequent, late-occurring infections.Objectives: To assess the prevalence and change in prevalence of early lower airway infections in a modern cohort of children with cystic fibrosis.Methods: All infants diagnosed with cystic fibrosis after newborn screening participating in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) cohort study between 2000 and 2018 were included. Participants prospectively underwent BAL at 3-6 months, 1 year, and annually up to 6 years of age. Lower airway infection prevalence was described. Changes in prevalence patterns were assessed longitudinally using generalized estimating equations controlling for age and repeated visits.Measurements and Main Results: A total of 380 infants underwent 1,759 BALs. The overall prevalence and median age of first acquisition of the most common infections were as follows: S. aureus, 11%, 2.5 years; P. aeruginosa, 8%, 2.4 years; Aspergillus species, 11%, 3.2 years; and H. influenzae, 9%, 3.1 years. During the study, a significant decrease in prevalence of P. aeruginosa (P < 0.001) and S. aureus (P < 0.001) was observed with a significant change toward more aggressive treatment. Prevalence of Aspergillus infections did not significantly change (P = 0.669).Conclusions:Aspergillus species and P. aeruginosa are commonly present in the lower airways from infancy. The decrease in prevalence of P. aeruginosa and S. aureus since 2000, coinciding with a more aggressive therapeutic approach, has resulted in Aspergillus becoming the most commonly isolated pathogen in young children. Further research is warranted to understand the implication of these findings.


Subject(s)
Aspergillosis/etiology , Cystic Fibrosis/complications , Cystic Fibrosis/physiopathology , Pseudomonas Infections/etiology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/etiology , Aspergillosis/epidemiology , Australia/epidemiology , Child, Preschool , Cohort Studies , Cystic Fibrosis/epidemiology , Female , Humans , Infant , Infant, Newborn , Male , Prevalence , Pseudomonas Infections/epidemiology
16.
Influenza Other Respir Viruses ; 13(1): 18-27, 2019 01.
Article in English | MEDLINE | ID: mdl-30137663

ABSTRACT

BACKGROUND: Influenza is a major cause of respiratory illness in young children. Assessing the impact of infection on children and the community is required to guide immunisation policies. OBJECTIVES: To describe the impact of laboratory-proven influenza in young children and to compare its impact with that of other respiratory viruses on the child, their family and the health care system. METHODS: Preschool children presenting for care or admission to a tertiary paediatric hospital during the 2008-2014 influenza seasons were tested for respiratory virus by polymerase chain reaction and culture. Parental surveys were used to determine the impact of infection on illness duration, medication use, absenteeism and health service utilisation. Multivariate regression analyses were used to assess the impact of influenza and to evaluate the association between influenza status and outcomes. RESULTS: Among 1191 children assessed, 238 had influenza. Among children with influenza, 87.8% were administered antipyretics and 40.9% antibiotics. 28.6% had secondary complications. 65.4% of children missed school/day care, and 53.4% of parents missed work. When influenza and other viruses were compared, significant differences were noted including duration of illness (influenza: 9.54 days, other viruses: 8.50 days; P = 0.005) and duration of absenteeism for both the child (23.1 vs 17.3 hours; P = 0.015) and their parents (28.5 vs 22.7 hours; P = 0.012). CONCLUSIONS: Influenza infection in young children has a significant impact on medication use, absenteeism and the use of health care service. Significant differences are identified when compared with other ILI. These data demonstrate that influenza prevention strategies including immunisation are likely to have wide and significant impacts.


Subject(s)
Absenteeism , Health Impact Assessment , Influenza, Human/epidemiology , Patient Acceptance of Health Care/statistics & numerical data , Australia/epidemiology , Child, Preschool , Cohort Studies , Female , Hospitals, Pediatric , Humans , Infant , Influenza, Human/drug therapy , Male , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Seasons , Surveys and Questionnaires
18.
PLoS One ; 12(10): e0186839, 2017.
Article in English | MEDLINE | ID: mdl-29065137

ABSTRACT

Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD). A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA) which are used to assign a Bexsero® antigen sequence type (BAST) to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA) were compared to those from the south-eastern seaboard (Victoria; VIC) from 2008 to 2012. Whole-genome sequencing (WGS) of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc) were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1-53.1%]) was significantly lower than that in VIC (66.4% [95% CI: 62.3-70.5%]). In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the need for representative surveillance when predicting potential impact of meningococcal B vaccines.


Subject(s)
Neisseria meningitidis/classification , Antigens, Bacterial/immunology , Genes, Bacterial , Humans , Neisseria meningitidis/genetics , Neisseria meningitidis/immunology , Victoria , Western Australia
19.
Br J Neurosurg ; 31(6): 672-676, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28835126

ABSTRACT

BACKGROUND: CSF infection is a significant complication of ventriculoperitoneal (VP) shunts and results in prolonged hospital stay, developmental delay and decreased quality of life. To decrease the high rates of neonatal VP shunt infections, an updated clinical guideline that included the use of antibiotic-impregnated shunts and a revised peri-operative antibiotic protocol was introduced in our neonatal unit. In this study, we evaluated the efficacy of these new guidelines in reducing the CSF shunt infection rates. METHODS: A retrospective cohort study of neonates (≤28 days) who had VP shunt insertions in our unit. RESULTS: 24 neonates in the first epoch received plain silastic shunt catheters (Feb 2002-April 2007), and 23 in the second epoch (August 2007-July 2015) received AIS catheters and a revised perioperative antibiotic protocol. Patient demographics were similar between both cohorts. Shunt related CSF infections were reduced in epoch 2 (2/23, 8.7%) compared to epoch 1 (5/24, 20.8%), but the results were not statistically significant (OR 0.36 (0.063-2.090); p = 0.256). Amongst neonates that needed VP shunt revision due to any cause, the median time interval between insertion to revision was significantly later in epoch 2 (epoch 1, 48 days (3-99); epoch 2, 148 days (20-396); p = 0.013). CONCLUSIONS: AIS catheters and a 48-hour perioperative antibiotic regimen may be beneficial in neonatal hydrocephalus. Adequately powered RCTs in the neonatal population are needed to confirm these findings.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Hydrocephalus/surgery , Prosthesis-Related Infections/prevention & control , Ventriculoperitoneal Shunt/methods , Catheters , Drug Implants , Female , Humans , Infant, Newborn , Length of Stay/statistics & numerical data , Male , Quality of Life , Retrospective Studies , Treatment Outcome
20.
Emerg Infect Dis ; 23(8): 1364-1367, 2017 08.
Article in English | MEDLINE | ID: mdl-28609259

ABSTRACT

In Western Australia, Neisseria meningitidis serogroup W clonal complex 11 became the predominant cause of invasive meningococcal disease in 2016. We used core-genome analysis to show emergence of a penicillin-resistant clade that had the penA_253 allele. This new penicillin-resistant clade might affect treatment regimens for this disease.


Subject(s)
Anti-Bacterial Agents/pharmacology , Meningococcal Infections/microbiology , Neisseria meningitidis/drug effects , Neisseria meningitidis/genetics , Penicillin Resistance/genetics , Penicillins/pharmacology , Humans , Meningococcal Infections/epidemiology , Microbial Sensitivity Tests , Neisseria meningitidis/classification , Phylogeny , Serogroup , Western Australia/epidemiology
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