This European Respiratory Society statement provides a comprehensive overview on protracted bacterial bronchitis (PBB) in children. A task force of experts, consisting of clinicians from Europe and ...Australia who manage children with PBB determined the overall scope of this statement through consensus. Systematic reviews addressing key questions were undertaken, diagrams in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement constructed and findings of relevant studies summarised. The final content of this statement was agreed upon by all members.The current knowledge regarding PBB is presented, including the definition, microbiology data, known pathobiology, bronchoalveolar lavage findings and treatment strategies to manage these children. Evidence for the definition of PBB was sought specifically and presented. In addition, the task force identified several major clinical areas in PBB requiring further research, including collecting more prospective data to better identify the disease burden within the community, determining its natural history, a better understanding of the underlying disease mechanisms and how to optimise its treatment, with a particular requirement for randomised controlled trials to be conducted in primary care.
Barcoded amplicon sequencing is rapidly becoming a standard method for profiling microbial communities, including the human respiratory microbiome. While this approach has less bias than standard ...cultivation, several steps can introduce variation including the type of DNA extraction method used. Here we assessed five different extraction methods on pediatric bronchoalveolar lavage (BAL) samples and a mock community comprised of nine bacterial genera to determine method reproducibility and detection limits for these typically low complexity communities. Additionally, using the mock community, we were able to evaluate contamination and select a relative abundance cut-off threshold based on the geometric distribution that optimizes the trade off between detecting bona fide operational taxonomic units and filtering out spurious ones. Using this threshold, the majority of genera in the mock community were predictably detected by all extraction methods including the hard-to-lyse Gram-positive genus Staphylococcus. Differences between extraction methods were significantly greater than between technical replicates for both the mock community and BAL samples emphasizing the importance of using a standardized methodology for microbiome studies. However, regardless of method used, individual patients retained unique diagnostic profiles. Furthermore, despite being stored as raw frozen samples for over five years, community profiles from BAL samples were consistent with historical culturing results. The culture-independent profiling of these samples also identified a number of anaerobic genera that are gaining acceptance as being part of the respiratory microbiome. This study should help guide researchers to formulate sampling, extraction and analysis strategies for respiratory and other human microbiome samples.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine if non‐pharmaceutical interventions (NPIs) impacted on respiratory virus detections in Queensland, Australia, during the COVID‐19 pandemic year of 2020.
We analysed weekly counts of ...influenza, human metapneumovirus, parainfluenza, respiratory syncytial virus, rhinovirus, and adenovirus available from a Queensland laboratory network for the year 2020. These were compared with averaged counts from 2015 to 2019.
Overall, 686,199 tests were performed. The timing of NPI implementation was associated with a sharp and sustained decline in influenza, where during the typical annual influenza season (weeks 23–40) no cases were detected from 163,296 tests compared with an average of 26.1% (11,844/45,396) of tests positive in 2015–2019. Similar results were observed for human metapneumovirus and parainfluenza. Respiratory syncytial virus detections also declined but increased in weeks 48–52 (5.6%; 562/10,078) to exceed the 2015–2019 average (2.9%; 150/5,018). Rhinovirus detections increased after schools reopened, peaking in weeks 23–27 (57.4%; 36,228/63,115), exceeding the 2017–2019 detections during that period (21.9%; 8,365/38,072).
NPIs implemented to control COVID‐19 were associated with altered frequency and proportions of respiratory virus detections.
NPIs derived from influenza pandemic plans were associated with profound decreases in influenza detections during 2020.
Pseudomonas aeruginosa is an opportunistic pathogen and an important cause of infection, particularly amongst cystic fibrosis (CF) patients. While specific strains capable of patient-to-patient ...transmission are known, many infections appear to be caused by unique and unrelated strains. There is a need to understand the relationship between strains capable of colonising the CF lung and the broader set of P. aeruginosa isolates found in natural environments. Here we report the results of a multilocus sequence typing (MLST)-based study designed to understand the genetic diversity and population structure of an extensive regional sample of P. aeruginosa isolates from South East Queensland, Australia. The analysis is based on 501 P. aeruginosa isolates obtained from environmental, animal and human (CF and non-CF) sources with particular emphasis on isolates from the Lower Brisbane River and isolates from CF patients obtained from the same geographical region. Overall, MLST identified 274 different sequence types, of which 53 were shared between one or more ecological settings. Our analysis revealed a limited association between genotype and environment and evidence of frequent recombination. We also found that genetic diversity of P. aeruginosa in Queensland, Australia was indistinguishable from that of the global P. aeruginosa population. Several CF strains were encountered frequently in multiple ecological settings; however, the most frequently encountered CF strains were confined to CF patients. Overall, our data confirm a non-clonal epidemic structure and indicate that most CF strains are a random sample of the broader P. aeruginosa population. The increased abundance of some CF strains in different geographical regions is a likely product of chance colonisation events followed by adaptation to the CF lung and horizontal transmission among patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Determining timing of first virus detection episodes (fVDEs) for different respiratory viruses in infants identifies risk periods and informs preventive interventions, including ...vaccination. We describe the ages and nature of fVDEs in an infant birth cohort and explore factors associated with increased odds of symptomatic fVDEs.
Methods
The Observational Research in Childhood Infectious Diseases (ORChID) study is a community-based birth cohort describing acute respiratory infections in infants until their second birthday. Parents recorded daily symptoms and collected nose swabs weekly, which were batch-tested using polymerase chain reaction assays for 17 respiratory viruses.
Results
One hundred fifty-eight infants participated in ORChID. The median age for fVDEs was 2.9 months for human rhinovirus (HRV) but was ≥13.9 months for other respiratory viruses. Overall, 52% of HRV fVDEs were symptomatic, compared with 57%–83% of other fVDEs. Respiratory syncytial virus and human metapneumovirus fVDEs were more severe than HRV fVDEs. Older age and the winter season were associated with symptomatic episodes.
Conclusions
Infants do not always experience respiratory symptoms with their fVDE. Predominance of early HRV detections highlights the need for timing any intervention early in life. fVDEs from other respiratory viruses most commonly occur when maternal vaccines may no longer provide protection.
In children, necrotizing pneumonia (NP) is an uncommon, severe complication of pneumonia. It is characterized by destruction of the underlying lung parenchyma resulting in multiple small, thin-walled ...cavities and is often accompanied by empyema and bronchopleural fistulae.
NP in children was first reported in children in 1994, and since then there has been a gradual increase in cases, which is partially explained by greater physician awareness and use of contrast computed tomography (CT) scans, and by temporal changes in circulating respiratory pathogens and antibiotic prescribing. The most common pathogens detected in children with NP are pneumococci and
. The underlying disease mechanisms are poorly understood, but likely relate to multiple host susceptibility and bacterial virulence factors, with viral-bacterial interactions also possibly having a role. Most cases are in previously healthy young children who, despite adequate antibiotic therapy for bacterial pneumonia, remain febrile and unwell. Many also have evidence of pleural effusion, empyema, or pyopneumothorax, which has undergone drainage or surgical intervention without clinical improvement. The diagnosis is generally made by chest imaging, with CT scans being the most sensitive, showing loss of normal pulmonary architecture, decreased parenchymal enhancement and multiple thin-walled cavities. Blood culture and culture and molecular testing of pleural fluid provide a microbiologic diagnosis in as many as 50% of cases. Prolonged antibiotics, draining pleural fluid and gas that causes mass effects, and maintaining ventilation, circulation, nutrition, fluid, and electrolyte balance are critical components of therapy. Despite its serious nature, death is uncommon, with good clinical, radiographic and functional recovery achieved in the 5-6 months following diagnosis. Increased knowledge of NP's pathogenesis will assist more rapid diagnosis and improve treatment and, ultimately, prevention.
It is important to consider that our understanding of NP is limited to individual case reports or small case series, and treatment data from randomized-controlled trials are lacking. Furthermore, case series are retrospective and usually confined to single centers. Consequently, these studies may not be representative of patients in other locations, especially when allowing for temporal changes in pathogen behaviour and differences in immunization schedules and antibiotic prescribing practices.
Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations ...in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease.
Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1-8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency 1-2 vs ≥3 episodes in the preceding 12 months) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066.
45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12-24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35-0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention.
Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.
National Health and Medical Research Council (Australia) and Health Research Council (New Zealand).
Objective To test the hypothesis that bacterial density, strain diversity, and concordance of pathogens between upper and lower airways are higher in children with bronchiectasis than in those with ...non-bronchiectatic conditions. Study design Nasopharyngeal (NP) swabs and bronchoalveolar lavage (BAL) fluid were cultured from 45 Indigenous children with bronchiectasis and 30 non-Indigenous children with non-bronchiectatic respiratory symptoms. Lower airway infection was defined as >104 colony-forming units of respiratory bacteria/mL of BAL fluid. Concordance was determined by phenotype or genotype. Results NP carriage of Streptococcus pneumoniae , nontypable Haemophilus influenzae (NTHi), and Moraxella catarrhalis , and lower airway infection by NTHi (47% vs 3%), were detected significantly more often in the children with bronchiectasis than in those without this condition. BAL specimens from the infected Indigenous children also showed greater strain diversity (71% vs 0%). Strain concordance in NP and BAL cultures was high in both infected subgroups. Conclusions The high density and diversity of respiratory bacteria, along with strain concordance between upper and lower airways, found in Indigenous children with bronchiectasis suggest a possible pathogenic role of recurrent aspiration of NP secretions.
PDF
