Association of antenatal and early childhood air pollution and greenspace exposures with respiratory pathogen upper airway acquisitions and respiratory health outcomes.

The association of air pollution and greenspace with respiratory pathogen acquisition and respiratory health was investigated in a community-based birth-cohort of 158 Australian children. Weekly nasal swabs and daily symptom-diaries were collected for 2-years, with annual reviews from ages 3-7-years. Annual exposure to fine-particulate-matter (PM2.5), nitrogen-dioxide (NO2), and normalised-difference-vegetation-index (NDVI) was estimated for pregnancy and the first 2-years-of-life. We examined rhinovirus, any respiratory virus, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae detections in the first 3-months-of-life, age at initial pathogen detection, wheezing in the first 2-years, and asthma at ages 5-7-years. Our findings suggest that higher NDVI was associated with fewer viral and M. catarrhalis detections in the first 3-months, while increased PM2.5 and NO2 were linked to earlier symptomatic rhinovirus and H. influenzae detections, respectively. However, no associations were observed with wheezing or asthma. Early-life exposure to air pollution and greenspace may influence early-life respiratory pathogen acquisition and illness. .

Interference Between Enteric Viruses and Live-Attenuated Rotavirus Vaccine Virus in a Healthy Australian Birth Cohort.

BACKGROUND: Rotavirus vaccines have reduced effectiveness in high-mortality settings. Interference between enteric viruses and live-attenuated oral vaccine strains may be a factor. METHODS: In a birth cohort of healthy Australian infants, parents collected weekly stool samples. Three hundred eighty-one paired swabs collected within 10-days of RotaTeq vaccination from 140 infants were tested for 10 enteric viruses and RotaTeq strains. RESULTS: Collectively, both ribonucleic acid and deoxyribonucleic acid viruses were negatively associated with RotaTeq shedding (adjusted odds ratio = 0.29, 95% confidence interval = 0.14-0.58 and adjusted odds ratio = 0.30, 95% confidence interval = 0.11-0.78, respectively). CONCLUSIONS: Enteric viruses may interfere with RotaTeq replication in the gut and thus RotaTeq stool shedding.

Novel Human Parechovirus 3 Diversity, Recombination, and Clinical Impact Across 7 Years: An Australian Story.

BACKGROUND: A novel human parechovirus 3 Australian recombinant (HPeV3-AR) strain emerged in 2013 and coincided with biennial outbreaks of sepsis-like illnesses in infants. We evaluated the molecular evolution of the HPeV3-AR strain and its association with severe HPeV infections. METHODS: HPeV3-positive samples collected from hospitalized infants aged 5-252 days in 2 Australian states (2013-2020) and from a community-based birth cohort (2010-2014) were sequenced. Coding regions were used to conduct phylogenetic and evolutionary analyses. A recombinant-specific polymerase chain reaction was designed and utilized to screen all clinical and community HPeV3-positive samples. RESULTS: Complete coding regions of 54 cases were obtained, which showed the HPeV3-AR strain progressively evolving, particularly in the 3' end of the nonstructural genes. The HPeV3-AR strain was not detected in the community birth cohort until the initial outbreak in late 2013. High-throughput screening showed that most (>75%) hospitalized HPeV3 cases involved the AR strain in the first 3 clinical outbreaks, with declining prevalence in the 2019-2020 season. The AR strain was not statistically associated with increased clinical severity among hospitalized infants. CONCLUSIONS: HPeV3-AR was the dominant strain during the study period. Increased hospital admissions may have been from a temporary fitness advantage and/or increased virulence.

Sapovirus Infections in an Australian Community-Based Healthy Birth Cohort During the First 2 Years of Life.

BACKGROUND: Sapovirus is an important cause of acute gastroenteritis (AGE) in young children. However, knowledge gaps remain in community settings. We investigated the epidemiology, disease characteristics, and healthcare use associated with sapovirus infections in Australian children during their first 2 years of life. METHODS: Children in the Brisbane-based Observational Research in Childhood Infectious Diseases birth cohort provided daily gastrointestinal symptoms (vomiting/loose stools), weekly stool swabs, and healthcare data until age 2 years. Swabs were batch-tested for sapovirus using real-time polymerase chain reaction assays. Incidence rates and estimates of associations were calculated. RESULTS: Overall, 158 children returned 11 124 swabs. There were 192 sapovirus infection episodes. The incidence rate in the first 2 years of life was 0.89 infections per child-year (95% confidence interval [CI], .76-1.05), and the symptomatic incidence rate was 0.26 episodes per child-year (95% CI, .17-.37). Age ≥6 months, the fall season, and childcare attendance increased disease incidence significantly. Fifty-four of the 180 (30%) infections with linked symptom diaries were symptomatic, with 72% recording vomiting and 48% diarrhea. Prior infection reduced risk of further infections (adjusted hazard ratio, 0.70 [95% CI, .54-.81]) in the study period. Viral loads were higher and viral shedding duration was longer in symptomatic than asymptomatic children. Twenty-three (43%) symptomatic episodes required healthcare, including 6 emergency department presentations and 2 hospitalizations. CONCLUSIONS: Sapovirus infections are common in Australian children aged 6-23 months. Efforts to reduce childhood AGE after the global rollout of rotavirus vaccines should include sapovirus where estimates of its incidence in communities will be crucial.

Human bocavirus-1 infections in Australian children aged < 2 years: a birth cohort study.

To determine human bocavirus-1 (HBoV1) infection characteristics in young Australian children. Data were from the Observational Research in Childhood Infectious Diseases (ORChID) study, a Brisbane, Australia-based birth cohort of healthy, term, newborns followed prospectively for 2 years. Parents recorded daily symptoms, maintained an illness-burden diary, and collected weekly nasal swabs, which were tested for 17 respiratory viruses, including HBoV1, by real-time polymerase chain reaction (PCR) assays. Main outcomes measured were infection incidence, risk factors, symptoms, and healthcare use. One hundred fifty-eight children in the ORChID cohort provided 11,126 weekly swabs, of which 157 swabs were HBoV1 positive involving 107 incident episodes. Co-detections were observed in 65/157 (41.4%) HBoV1-positive swabs (or 41/107 [38.3%] infection episodes), principally with rhinovirus. Shedding duration was 1 week in 64.5% of episodes. The incidence of HBoV1 infections in the first 2 years of life was 0.58 episodes per child-year (95% confidence interval [CI] 0.47-0.71), including 0.38 episodes per child-year (95% CI 0.30-0.49) associated with respiratory symptoms. Recurrent episodes occurred in 18/87 (20.7%) children following their primary infection. In the first 2 years of life, incidence of HBoV1 episodes increased with age, during winter and with childcare attendance. Overall, 64.2% of HBoV1 episodes were symptomatic, with 26.4% having healthcare contact. Viral load estimates were higher when children were symptomatic than when asymptomatic (mean difference = 3.4; 95% CI 1.0-5.7 PCR cycle threshold units). After age 6 months, HBoV1 is detected frequently in the first 2 years of life, especially during winter. Symptoms are usually mild and associated with higher viral loads.

Thoracic Society of Australia and New Zealand (TSANZ) position statement on chronic suppurative lung disease and bronchiectasis in children, adolescents and adults in Australia and New Zealand.

This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.

Characterization of the Phase-Variable Autotransporter Lav Reveals a Role in Host Cell Adherence and Biofilm Formation in Nontypeable Haemophilus influenzae.

Lav is an autotransporter protein found in pathogenic Haemophilus and Neisseria species. Lav in nontypeable Haemophilus influenzae (NTHi) is phase-variable: the gene reversibly switches ON-OFF via changes in length of a locus-located GCAA(n) simple DNA sequence repeat tract. The expression status of lav was examined in carriage and invasive collections of NTHi, where it was predominantly not expressed (OFF). Phenotypic study showed lav expression (ON) results in increased adherence to human lung cells and denser biofilm formation. A survey of Haemophilus species genome sequences showed lav is present in ∼60% of NTHi strains, but lav is not present in most typeable H. influenzae strains. Sequence analysis revealed a total of five distinct variants of the Lav passenger domain present in Haemophilus spp., with these five variants showing a distinct lineage distribution. Determining the role of Lav in NTHi will help understand the role of this protein during distinct pathologies.

European Respiratory Society statement for defining respiratory exacerbations in children and adolescents with bronchiectasis for clinical trials.

Bronchiectasis is being diagnosed increasingly in children and adolescents. Recurrent respiratory exacerbations are common in children and adolescents with this chronic pulmonary disorder. Respiratory exacerbations are associated with an impaired quality of life, poorer long-term clinical outcomes, and substantial costs to the family and health systems. The 2021 European Respiratory Society (ERS) clinical practice guideline for the management of children and adolescents with bronchiectasis provided a definition of acute respiratory exacerbations for clinical use but to date there is no comparable universal definition for clinical research. Given the importance of exacerbations in the field, this ERS Task Force sought to obtain robust definitions of respiratory exacerbations for clinical research. The panel was a multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, methodology, patient advocacy, and parents of children and adolescents with bronchiectasis. We used a standardised process that included a systematic literature review, parent survey, and a Delphi approach involving 299 physicians (54 countries) caring for children and adolescents with bronchiectasis. Consensus was obtained for all four statements drafted by the panel as the disagreement rate was very low (range 3.6-7.2%). The panel unanimously endorsed the four consensus definitions for 1a) non-severe exacerbation and 1b) severe exacerbation as an outcome measure, 2) non-severe exacerbation for studies initiating treatment, and 3) resolution of a non-severe exacerbation for clinical trials involving children and adolescents with bronchiectasis. This ERS Task Force proposes using these internationally derived, consensus-based definitions of respiratory exacerbations for future clinical paediatric bronchiectasis research.

The Initial Timing and Burden of Viral Gastrointestinal Infections in Australian Infants: A Birth Cohort Study.

ABSTRACT: The timing and nature of initial infections by potentially vaccine-preventable gastrointestinal viruses (group-F adenoviruses, classic human astrovirus, norovirus I/II, and sapovirus I/II/IV/V) was investigated in a community-based birth cohort. Weekly stool samples were collected from 158 children aged <2 years in an Australian subtropical city. Median age at initial infection was lowest for norovirus II (13.8 months) followed by sapovirus (14.3 months) and classic human astrovirus (17.6 months), and was >24 months for the remaining viruses. Norovirus II and sapovirus were most often associated with acute gastroenteritis symptoms (57% and 44%, respectively). Overall, healthcare was sought for 45% of symptomatic initial infections, which varied between 17% for norovirus I to 55% for norovirus II. Age at initial infection was lower when participants were exposed to other children. Norovirus II and sapovirus were the most important pathogens in this cohort, providing further evidence for them being priority targets for vaccine development.

Streptococcus anginosus group infections in hospitalised children and young people.

AIM: The Streptococcus anginosus group (SAG) comprises three bacterial species colonising the mouth and gastrointestinal and genitourinary tracts and capable of serious pyogenic infections. Although well-described in adults, studies in children are limited. Here, we characterise paediatric SAG infections from a single Australian centre. METHODS: Hospitalised patients aged ≤18 years with positive SAG cultures from January 2009 to December 2019 were identified from Pathology Queensland's Gold Coast Laboratory database and their medical records were reviewed. RESULTS: Two-hundred children (62% male), median age 12 years (interquartile range 6-16), with positive SAG cultures were identified. Overall, 90% received intravenous antibiotics, 89% underwent surgical drainage, 23% were readmitted and 15% required additional surgery. The most common sites were the abdomen (39%), soft tissues (36%) and head and neck regions (21%). Since 2011, Pathology Queensland reported SAG at the species level (n = 133). Of these, S. anginosus was the most prevalent (39%), then S. constellatus (34%) and S. intermedius (27%). Compared with the other two species, S. intermedius was most commonly associated with head and neck infections (relative risk (RR) = 2.2, 95% confidence interval (CI) 1.4-3.5), while S. constellatus (RR = 1.7, 95% CI 1.2-2.4) and S. anginosus (RR = 1.5, 95% CI 1.0-2.0) were each associated with a higher risk of intra-abdominal infection than S. intermedius. Since February 2015, the number of children admitted with SAG-associated intra-abdominal infection per 1000 hospitalisations increased by 29% annually compared with an annual decline of 8% in previous years. CONCLUSIONS: SAG infections occur at various anatomical sites. Despite antibiotics and surgical management, almost one-quarter are re-hospitalised for further treatment.

European Respiratory Society guidelines for the management of children and adolescents with bronchiectasis.

There is increasing awareness of bronchiectasis in children and adolescents, a chronic pulmonary disorder associated with poor quality of life for the child/adolescent and their parents, recurrent exacerbations, and costs to the family and health systems. Optimal treatment improves clinical outcomes. Several national guidelines exist, but there are no international guidelines.The European Respiratory Society (ERS) Task Force for the management of paediatric bronchiectasis sought to identify evidence-based management (investigation and treatment) strategies. It used the ERS standardised methodology that included a systematic review of the literature and application of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to define the quality of the evidence and level of recommendations.A multidisciplinary team of specialists in paediatric and adult respiratory medicine, infectious disease, physiotherapy, primary care, nursing, radiology, immunology, methodology, patient advocacy and parents of children/adolescents with bronchiectasis considered the most relevant clinical questions (for both clinicians and patients) related to managing paediatric bronchiectasis. 14 key clinical questions (seven PICO (Patient, Intervention, Comparison, Outcome) and seven narrative) were generated. The outcomes for each PICO were decided by voting by the panel and parent/patient advisory group.This guideline addresses the definition, diagnostic approach and antibiotic treatment of exacerbations, pathogen eradication, long-term antibiotic therapy, asthma-type therapies (inhaled corticosteroids and bronchodilators), mucoactive drugs, airway clearance, investigation of underlying causes of bronchiectasis, disease monitoring, factors to consider before surgical treatment, and the reversibility and prevention of bronchiectasis in children/adolescents. Benchmarking quality of care for children/adolescents with bronchiectasis to improve clinical outcomes and evidence gaps for future research could be based on these recommendations.

Epidemiology of respiratory syncytial virus in a community birth cohort of infants in the first 2 years of life.

Respiratory syncytial virus (RSV) is the most common virus identified in children hospitalised with acute respiratory infections. However, less is known about RSV in community settings. This report describes RSV epidemiology in the community, including acute illness episodes, healthcare burden, and risk factors in Australian children during the first 2-years of life. A community-based, birth cohort from Brisbane, Australia, followed children until their second birthday. Parents completed daily respiratory symptom and illness-burden diaries. Weekly parent-collected nasal swabs were analysed for RSV by real-time polymerase chain reaction assays. Serum RSV-neutralising antibodies were assayed at age 3 years. Overall, 158 children provided 11,216 swabs, of which 104 were RSV-positive (85 incident episodes). RSV incidence in the first 2 years of life was 0.46 (95% CI = 0.37-0.58) episodes per child-year. Incidence increased with age and formal childcare attendance and was highest in autumn. Of 82 episodes linked with symptom data, 60 (73.2%) were symptomatic, 28 (34.1%) received community-based medical care, and 2 (2.4%) led to hospitalisation. Viral load was higher in symptomatic than asymptomatic infections. In 72 children, RSV-specific antibody seroprevalence was 94.4% at age 3 years.Conclusion: RSV incidence increased after age 6-months with approximately three-quarters of infections symptomatic and most infections treated in the community. What is known •RSV is a major cause of hospitalisation for acute lower respiratory infections in infants and young children, especially in the first 6 months of life. •However, limited data exist on the overall burden in young children at the community level. What is new •RSV incidence in the community increases after age 6 months, and by 3 years, most children have been infected. •About one-quarter of RSV infections were asymptomatic in children aged < 2 years, and approximately 60% of children with RSV-related symptoms had a healthcare contact of any kind with most managed within the community.

Community-level burden of acute diarrhoeal illness in the first 2 years of life in Brisbane, Australia: A birth cohort study.

AIM: This study sought to describe the burden of acute diarrhoeal illness (ADI) in an Australian subtropical urban setting following rotavirus vaccine introduction and to investigate the associations between child/family characteristics and ADI. METHODS: Parents of 154 children from the Observational Research in Childhood Infectious Diseases birth cohort provided daily symptom and health-care data until the age of 2 years. RESULTS: The incidence rate of ADI was 1.07 per child-year (95% confidence interval: 0.94-1.21). The median length of episode duration was 3 days (25th-75th percentiles: 1-6). The incidence rate was significantly higher in the first month of life and between 6 and 17 months of age compared with 18-23 months, also for children with siblings and in formal childcare. Overall, 49% of ADI episodes led to health-care visits. CONCLUSIONS: Despite a successful rotavirus vaccine programme, ADI still results in a substantial disease burden affecting young Australian children and their families.

Parechovirus A Infections in Healthy Australian Children During the First 2 Years of Life: A Community-based Longitudinal Birth Cohort Study.

BACKGROUND: Hospital-based studies identify parechovirus (PeV), primarily PeV-A3, as an important cause of severe infections in young children. However, few community-based studies have been published and the true PeV infection burden is unknown. We investigated PeV epidemiology in healthy children participating in a community-based, longitudinal birth cohort study. METHODS: Australian children (n = 158) enrolled in the Observational Research in Childhood Infectious Diseases (ORChID) study were followed from birth until their second birthday. Weekly stool and nasal swabs and daily symptom diaries were collected. Swabs were tested for PeV by reverse-transcription polymerase chain reaction and genotypes determined by subgenomic sequencing. Incidence rate, infection characteristics, clinical associations, and virus codetections were investigated. RESULTS: PeV was detected in 1423 of 11 124 (12.8%) and 17 of 8100 (0.2%) stool and nasal swabs, respectively. Major genotypes among the 306 infection episodes identified were PeV-A1 (47.9%), PeV-A6 (20.1%), and PeV-A3 (18.3%). The incidence rate was 144 episodes (95% confidence interval, 128-160) per 100 child-years. First infections appeared at a median age of 8 (interquartile range, 6.0-11.7) months. Annual seasonal peaks changing from PeV-A1 to PeV-A3 were observed. Infection was positively associated with age ≥6 months, summer season, nonexclusive breastfeeding at age <3 months, and formal childcare attendance before age 12 months. Sole PeV infections were either asymptomatic (38.4%) or mild (32.7%), while codetection with other viruses in stool swabs was common (64.4%). CONCLUSIONS: In contrast with hospital-based studies, this study showed that diverse and dynamically changing PeV genotypes circulate in the community causing mild or subclinical infections in children.Parechovirus can cause severe illnesses in children. However, studies focus mainly on hospitalized populations. True disease burden in the community remains largely unknown. From our community-based cohort, we found diverse parechovirus genotypes in the community, causing mild or subclinical infections in children. CLINICAL TRIALS REGISTRATION: NCT01304914.

Over-diagnosis of Rotavirus Infection in Infants Due to Detection of Vaccine Virus.

An accurate rotavirus diagnosis is important for clinical management and monitoring active disease and vaccine effectiveness. Between 2016-2018, rotavirus-positive results in our laboratory were from vaccine virus shedding in 71/152 (46.7%) infants with a request for rotavirus testing. Routine infant diagnostic testing should ideally distinguish vaccine from wild-type viruses.

Pharmacodynamic Evaluation of Plasma and Epithelial Lining Fluid Exposures of Amikacin against Pseudomonas aeruginosa in a Dynamic In Vitro Hollow-Fiber Infection Model.

Given that aminoglycosides, such as amikacin, may be used for multidrug-resistant Pseudomonas aeruginosa infections, optimization of therapy is paramount for improved treatment outcomes. This study aims to investigate the pharmacodynamics of different simulated intravenous amikacin doses on susceptible P. aeruginosa to inform ventilator-associated pneumonia (VAP) and sepsis treatment choices. A hollow-fiber infection model with two P. aeruginosa isolates (MICs of 2 and 8 mg/liter) with an initial inoculum of ∼108 CFU/ml was used to test different amikacin dosing regimens. Three regimens (15, 25, and 50 mg/kg) were tested to simulate a blood exposure, while a 30 mg/kg regimen simulated the epithelial lining fluid (ELF) for potential respiratory tract infection. Data were described using a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model. Whole-genome sequencing was used to identify mutations associated with resistance emergence. While bacterial density was reduced by >6 logs within the first 12 h in simulated blood exposures following this initial bacterial kill, there was amplification of a resistant subpopulation with ribosomal mutations that were likely mediating amikacin resistance. No appreciable bacterial killing occurred with subsequent doses. There was less (<5 log) bacterial killing in the simulated ELF exposure for either isolate tested. Simulation studies suggested that a dose of 30 and 50 mg/kg may provide maximal bacterial killing for bloodstream and VAP infections, respectively. Our results suggest that amikacin efficacy may be improved with the use of high-dose therapy to rapidly eliminate susceptible bacteria. Subsequent doses may have reduced efficacy given the rapid amplification of less-susceptible bacterial subpopulations with amikacin monotherapy.

Early markers of cystic fibrosis structural lung disease: follow-up of the ACFBAL cohort.

Little is known about early predictors of later cystic fibrosis (CF) structural lung disease. This study examined early predictors of progressive structural lung abnormalities in children who completed the Australasian CF Bronchoalveolar Lavage (ACFBAL) clinical trial at age 5-years and participated in an observational follow-up study (CF-FAB).Eight Australian and New Zealand CF centres participated in CF-FAB and provided follow-up chest computed-tomography (CT) scans for children who had completed the ACFBAL study with baseline scans at age 5-years. CT scans were annotated using PRAGMA-CF scoring. Ordinal regression analysis and linear regression were used to investigate associations between PRAGMA-CF (Perth-Rotterdam Annotated Grid Morphometric Analysis for CF) outcomes at follow-up and variables measured during the ACFBAL study.99 out of 157 ACFBAL children (mean±sd age 13±1.5 years) participated in the CF-FAB study. The probability of bronchiectasis at follow-up increased with airway disease severity on the baseline CT scan. In multiple regression (retaining factors at p<0.05) the extent of bronchiectasis at follow-up was associated with baseline atelectasis (OR 7.2, 95% CI 2.4-22; p≤ 0.001), bronchoalveolar lavage (BAL) log2 interleukin (IL)-8 (OR 1.2, 95% CI 1.05-1.5; p=0.010) and body mass index z-score (OR 0.49, 95% CI 0.24-1.00; p=0.05) at age 5 years. Percentage trapped air at follow-up was associated with BAL log2 IL-8 (coefficient 1.3, 95% CI 0.57-2.1; p<0.001) at age 5 years.The extent of airway disease, atelectasis, airway inflammation and poor nutritional status in early childhood are risk factors for progressive structural lung disease in adolescence.

Effect of Definitions of Acute Gastroenteritis Episodes Using Symptom Diaries in Paediatric Cohorts: A Systematic Review.

Estimates of acute gastroenteritis (AGE) burden are difficult to compare between studies because of inconsistent definitions describing this illness. AGE definitions used in prospective, community-based childhood cohort studies were identified by searching databases for studies that collected daily observations of AGE symptoms. Disease definitions and refractory periods were extracted. Data from the Australian community-based Observational Research in Childhood Infectious Diseases birth cohort were used to calculate AGE incidence and duration using identified AGE definitions, and the World Health Organization definition for diarrhoea. Eight distinct AGE definitions were identified. All included loose stools and 7 included vomiting as symptoms. The refractory period separating episodes ranged from 1 to 21 days. When applied to the Observational Research in Childhood Infectious Diseases dataset, AGE incidence ranged from 0.8 to 2.6 episodes per child-year-at-risk, a 3-fold relative difference. Direct comparisons of rates from different cohorts can only be undertaken if a standard definition for AGE is adopted.

Cost of hospitalization for bronchiectasis exacerbation in children.

BACKGROUND AND OBJECTIVE: Despite paediatric bronchiectasis being recognized increasingly worldwide, prior reports of hospitalization costs for bronchiectasis in children are lacking. This study aimed to (i) identify health service costs of hospitalizations and (ii) factors associated with these costs in children admitted to an Australian paediatric hospital following an acute exacerbation of their bronchiectasis. METHODS: Demographic and hospital resource use data were prospectively recorded for 100 hospitalizations in 80 children aged <18 years admitted consecutively to the QCH, Brisbane, Australia. Costs (2016 AUD) were obtained from the hospital's Finance Department. Linear regressions, with bootstrap resampling to quantify uncertainty, were used to estimate factors affecting cost of hospitalization. RESULTS: The 100 hospitalizations (48 males) had a median (IQR) age of 6.04 (4.04-9.85) years. Their mean (SD) LOS was 12.30 (4.60) days. The mean (SD) direct health service cost was AUD 30 182 (13 998) per hospitalization. The greatest contributor to costs was health professional wages, accounting for 70% of the cost per episode. LOS, younger age at admission and number of bronchiectatic lobes affected were associated with higher costs, whilst HITH service was associated with lower cost. The cost to families on average was AUD 2669.50 (SD: 991.50) per hospitalization when accounting for lost wages and opportunity cost. CONCLUSION: The per episode healthcare cost burden of hospitalizations for paediatric bronchiectasis exacerbations is substantial. Interventions that prevent hospitalized exacerbations and reduce severity of childhood bronchiectasis with even moderate effectiveness are likely to result in substantial hospital costs savings.

Analysis of Invasive Nontypeable Haemophilus influenzae Isolates Reveals Selection for the Expression State of Particular Phase-Variable Lipooligosaccharide Biosynthetic Genes.

Nontypeable Haemophilus influenzae (NTHi) is a major human pathogen, responsible for several acute and chronic infections of the respiratory tract. The incidence of invasive infections caused by NTHi is increasing worldwide. NTHi is able to colonize the nasopharynx asymptomatically, and the exact change(s) responsible for transition from benign carriage to overt disease is not understood. We have previously reported that phase variation (the rapid and reversible ON-OFF switching of gene expression) of particular lipooligosaccharide (LOS) glycosyltransferases occurs during transition from colonizing the nasopharynx to invading the middle ear. Variation in the structure of the LOS is dependent on the ON/OFF expression status of each of the glycosyltransferases responsible for LOS biosynthesis. In this study, we surveyed a collection of invasive NTHi isolates for ON/OFF expression status of seven phase-variable LOS glycosyltransferases. We report that the expression state of the LOS biosynthetic genes oafA ON and lic2A OFF shows a correlation with invasive NTHi isolates. We hypothesize that these gene expression changes contribute to the invasive potential of NTHi. OafA expression, which is responsible for the addition of an O-acetyl group onto the LOS, has been shown to impart a phenotype of increased serum resistance and may serve as a marker for invasive NTHi.