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High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection.

ABSTRACT: The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing ("meta-transcriptomics") to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease.

SUBMITTER: Li CX

PROVIDER: S-EPMC7054269 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection.

Li Ci-Xiu CX Li Wei W Zhou Jun J Zhang Bing B Feng Yan Y Xu Chang-Ping CP Lu Yi-Yu YY Holmes Edward C EC Shi Mang M

Scientific reports 20200303 1

The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing ("meta-transcriptomics") to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence ...[more]

PMID: 32127629

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Project description:BackgroundHigh-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS.MethodsPatients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.ResultsA total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference - 1.3 (95%CI - 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [- 2.5 (95%CI - 4.9, - 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS.ConclusionThe use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.

Project description:BackgroundFor years, paediatric critical care practitioners used the adult American European Consensus Conference (AECC) and revised Berlin Definition (BD) for acute respiratory distress syndrome (ARDS) to study the epidemiology of paediatric ARDS (PARDS). In 2015, the paediatric specific definition, Paediatric Acute Lung Injury Consensus Conference (PALICC) was developed. The use of non-invasive metrics of oxygenation to stratify disease severity were introduced in this definition, although this potentially may lead to a confounding effect of disease severity since it is more common to place indwelling arterial lines in sicker patients. We tested the hypothesis that PALICC outperforms AECC/BD in our high acuity PICU, which employs a liberal use of indwelling arterial lines and high-frequency oscillatory ventilation (HFOV).MethodsWe retrospectively collected data from children < 18 years mechanically ventilated for at least 24 h in our tertiary care, university-affiliated paediatric intensive care unit. The primary endpoint was the difference in the number of PARDS cases between AECC/BD and PALICC. Secondary endpoints included mortality and ventilator free days. Performance was assessed by the area under the receiver operating characteristics curve (AUC-ROC).ResultsData from 909 out of 2433 patients was eligible for analysis. AECC/BD identified 35 (1.4%) patients (mortality 25.7%), whereas PALICC identified 135 (5.5%) patients (mortality 14.1%). All but two patients meeting AECC/Berlin criteria were also identified by PALICC. Almost half of the cohort (45.2%) had mild, 33.3% moderate and 21.5% severe PALICC PARDS at onset. Highest mortality rates were seen in patients with AECC acute lung injury (ALI)/mild Berlin and severe PALICC PARDS. The AUC-ROC for Berlin was the highest 24 h (0.392 [0.124-0.659]) after onset. PALICC showed the highest AUC-ROC at the same moment however higher than Berlin (0.531 [0.345-0.716]). Mortality rates were significantly increased in patients with bilateral consolidations (9.3% unilateral vs 26.3% bilateral, p = 0.025).ConclusionsPALICC identified more new cases PARDS than the AECC/Berlin definition. However, both PALICC and Berlin performed poorly in terms of mortality risk stratification. The presence of bilateral consolidations was associated with a higher mortality rate. Our findings may be considered in future modifications of the PALICC criteria.

Project description:IntroductionAcute hypoxaemic respiratory failure (AHRF) in children is the most frequent reason for non-elective hospital admission. During the initial phase, AHRF is a clinical syndrome defined for the purpose of this study by an oxygen requirement and caused by pneumonia, lower respiratory tract infections, asthma or bronchiolitis. Up to 20% of these children with AHRF can rapidly deteriorate requiring non-invasive or invasive ventilation. Nasal high-flow (NHF) therapy has been used by clinicians for oxygen therapy outside intensive care settings to prevent escalation of care. A recent randomised trial in infants with bronchiolitis has shown that NHF therapy reduces the need to escalate therapy. No similar data is available in the older children presenting with AHRF. In this study we aim to investigate in children aged 1 to 4 years presenting with AHRF if early NHF therapy compared with standard-oxygen therapy reduces hospital length of stay and if this is cost-effective compared with standard treatment.Methods and analysisThe study design is an open-labelled randomised multicentre trial comparing early NHF and standard-oxygen therapy and will be stratified by sites and into obstructive and non-obstructive groups. Children aged 1 to 4 years (n=1512) presenting with AHRF to one of the participating emergency departments will be randomly allocated to NHF or standard-oxygen therapy once the eligibility criteria have been met (oxygen requirement with transcutaneous saturation <92%/90% (dependant on hospital standard threshold), diagnosis of AHRF, admission to hospital and tachypnoea ?35 breaths/min). Children in the standard-oxygen group can receive rescue NHF therapy if escalation is required. The primary outcome is hospital length of stay. Secondary outcomes will include length of oxygen therapy, proportion of intensive care admissions, healthcare resource utilisation and associated costs. Analyses will be conducted on an intention-to-treat basis.Ethics and disseminationEthics approval has been obtained in Australia (HREC/15/QRCH/159) and New Zealand (HDEC 17/NTA/135). The trial commenced recruitment in December 2017. The study findings will be submitted for publication in a peer-reviewed journal and presented at relevant conferences. Authorship of all publications will be decided by mutual consensus of the research team.Trial registration numberACTRN12618000210279.

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High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection.

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High resolution metagenomic characterization of complex infectomes in paediatric acute respiratory infection.

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