Risk Factors and Clinical Prognosis Associated With RSV-ALRI Intensive Care Unit Admission in Children <2 Years of Age: A Multicenter Study.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections (ALRIs) in children <2 years of age. Currently, there are limited data on risk factors for very severe RSV-ALRI requiring intensive care unit (ICU) admission. METHODS: We conducted a case-control study of children <2 years old admitted with RSV-ALRI to the Sydney Children's Hospital Network, comprising 2 large tertiary pediatric hospitals. Cases were children with laboratory-confirmed RSV-ALRI admitted to ICU, and controls were (1:2, matched on date of admission) children hospitalized with RSV-ALRI but not requiring ICU transfer. Data on risk factors were retrieved from the electronic medical record system. Adjusted odds ratios (aORs) with 95% confidence intervals (95% CI) associated with risk factors for ICU admission and the association with clinical and treatment factors were determined from logistic regression models. RESULTS: A total of 44 (44%) of 100 cases and 90 (48.1%) of 187 controls were male. Age <6 months and preterm births were associated with a 2.10-fold (95% CI: 1.14-3.79) and 2.35-fold (95% CI: 1.26-4.41) increased risk in ICU admissions, respectively. The presence of any chronic health condition was a significant risk factor for ICU admission. The clinical presentations on admission more commonly seen in cases were apnea (aOR: 5.01, 95% CI: 1.50-17.13) and respiratory distress (aOR: 15.91, 95% CI: 4.52-55.97). Cases were more likely to be hospitalized for longer duration and require respiratory support. CONCLUSIONS: Our results can be translated into a clinical risk algorithm to identify children at risk of very severe RSV disease.

Variation in clinical practice guidelines for use of palivizumab in preventing severe respiratory syncytial viral (RSV) disease in high-risk infants.

BACKGROUND: Uniformity and compliance with clinical practice guidelines (CPGs) for use of palivizumab in preventing severe respiratory syncytial viral infection in Australian high-risk infants remain unclear. METHODS: An online survey was conducted across the Australian and New Zealand Neonatal Network (ANZNN) to determine clinical practices around palivizumab. A literature search was also performed to identify and compare national and international guidelines. RESULTS: A total of 65 of 422 ANZNN members completed the survey. Respondents included 61 senior medical staff of consultants/staff specialists (78%) and four nursing staff (6%). According to the survey, infants most likely to be recommended palivizumab included preterm infants born <29 weeks gestational age (GA) (30%), children with chronic lung diseases (CLDs) born <32 weeks GA (40%), and with hemodynamically significant heart disease (35%). Many of the respondents (53%) stated that CPGs for palivizumab were developed locally. Literature search identified 20 guidelines (10 international and 10 domestic); 16 (80%) recommended palivizumab use in preterm infants, 16 (80%) recommended use in infants with CLD, 17 (85%) in congenital heart disease and 6 (30%) in bronchopulmonary dysplasia (BPD). Eight (40%) guidelines provided specific recommendations for immunocompromised infants. Canada, Western Australia, and American Academy of Paediatrics provided recommendations for Indigenous children. Frequency and dosage of palivizumab was universal across all CPGs. None of the international guidelines obtained were from low- or middle-income countries. CONCLUSIONS: Standardization of CPGs may improve clinical decision making around use of palivizumab in high-risk infants.

COVID-19 in New South Wales children during 2021: severity and clinical spectrum.

OBJECTIVES: To describe the severity and clinical spectrum of coronavirus disease 2019 (COVID-19) in children during the 2021 New South Wales outbreak of the Delta variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). DESIGN, SETTING: Prospective cohort study in three metropolitan Sydney local health districts, 1 June - 31 October 2021. PARTICIPANTS: Children under 16 years of age with positive SARS-CoV-2 nucleic acid test results admitted to hospital or managed by the Sydney Children's Hospital Network (SCHN) virtual care team. MAIN OUTCOME MEASURES: Age-specific SARS-CoV-2 infection frequency, overall and separately for SCHN virtual and hospital patients; rates of medical and social reason admissions, intensive care admissions, and paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 per 100 SARS-CoV-2 infections; demographic and clinical factors that influenced likelihood of hospital admission. RESULTS: A total of 17 474 SARS-CoV-2 infections in children under 16 were recorded in NSW, of whom 11 985 (68.6%) received SCHN-coordinated care, including 459 admitted to SCHN hospitals: 165 for medical reasons (1.38 [95% CI, 1.17-1.59] per 100 infections), including 15 admitted to intensive care, and 294 (under 18 years of age) for social reasons (2.45 [95% CI, 2.18-2.73] per 100 infections). In an analysis that included all children admitted to hospital and a random sample of those managed by the virtual team, having another medical condition (adjusted odds ratio [aOR], 7.42; 95% CI, 3.08-19.3) was associated with increased likelihood of medical admission; in univariate analyses, non-asthmatic chronic respiratory disease was associated with greater (OR, 9.21; 95% CI, 1.61-174) and asthma/viral induced wheeze with lower likelihood of admission (OR, 0.38; 95% CI, 0.18-0.78). The likelihood of admission for medical reasons declined from infancy to 5-11 years, but rose again for those aged 12-15 years. Sex and Indigenous status did not influence the likelihood of admission. CONCLUSION: Most SARS-CoV-2 infections (Delta variant) in children were asymptomatic or associated with mild disease. Hospitalisation was relatively infrequent, and most common for infants, adolescents, and children with other medical conditions. More children were hospitalised for social than for medical reasons.

RSV Epidemiology in Australia Before and During COVID-19.

COVID-19 public health measures altered respiratory syncytial virus (RSV) epidemiology. We examined age-stratified trends in RSV-related disease in Australian children in 2020 compared with previous years.

Respiratory Syncytial Virus-attributable Deaths in a Major Pediatric Hospital in New South Wales, Australia, 1998-2018.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and an important contributor to child mortality. In this study, we estimated the frequency and described the clinical features of RSV-attributable deaths in Australian children. METHODS: We conducted a retrospective observational study of RSV-associated deaths in hospitalized children <16 years of age over a 21-year period (1998-2018) in a pediatric tertiary/quaternary referral hospital in New South Wales (NSW), Australia. RSV-associated deaths were identified, reviewed, and classified according to RSV contribution to death. For 'RSV-attributable' deaths, we estimated frequency, case fatality ratio (CFR), and population death rate. We described demographic and clinical features of cases. RESULTS: There were 20 RSV-attributable deaths. RSV was considered the primary cause of death for five cases and a contributory cause for 15 cases. The CFR among hospitalized cases was 0.2% (20/9779). The annual death rate was 0.6 per 10,000 hospitalized children. The population death rate was 1.2 (95% confidence interval 0.5-2.7) per million children <16 years of age in NSW. The median age at death was 28.7 months (interquartile range 8.8-75.0). All children had at least one medical comorbidity. Over half the deaths occurred in children ≥2 years of age (11, 55%). RSV healthcare-associated infection (RSV-HAI) was common (11, 55%). CONCLUSIONS: RSV-attributable death is infrequent in this setting. Deaths occurred exclusively in children with medical comorbidity and a high proportion were RSV-HAI. Children with medical comorbidity, including those ≥2 years of age, should be prioritized for targeted prevention of RSV disease.

Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series.

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.

Respiratory syncytial virus subtype circulation and associated disease severity at an Australian paediatric referral hospital, 2014-2018.

AIM: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections in children and the development of vaccines to protect at-risk groups is a global priority. The aim of this study was to describe RSV subtype circulation patterns and associated disease severity to inform on potential impact of an RSV-specific prevention strategy. METHODS: Single-centre retrospective observational study of children aged <16 years with laboratory-confirmed RSV infection from 2014 to 2018 inclusive. We described the features and frequency of all RSV subtype detections. We selected a random sample of RSV-A and RSV-B cases from each year (n = 200), described demographic and clinical features of these cases, and compared indicators of disease severity between subtypes. RESULTS: We identified 3591 RSV detections over a 5-year period and found consistent co-circulation of subtypes with alternating predominance. Demographic and clinical characteristics were similar between children presenting with RSV-A and RSV-B infections. There was no difference in indicators of severity between the subtypes except for paediatric intensive care unit length of stay which was longer in the RSV-B group (3 vs. 5 days, P = 0.006). Respiratory co-infections were more frequent in the RSV-B group (41.8% vs. 27.4%, P = 0.035). When these were excluded there was no longer a detectable difference in paediatric intensive care unit length of stay. CONCLUSIONS: We found co-circulation of RSV subtypes and no convincing evidence of a difference in disease severity between subtypes. RSV-specific interventions will need to be equally effective against both RSV-A and RSV-B to have the greatest impact on reducing severe RSV disease in this population.

Paediatric Active Enhanced Disease Surveillance (PAEDS) 2017 and 2018: Prospective hospital-based surveillance for serious paediatric conditions.

Introduction: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine-preventable diseases and potential adverse events following immunisation (AEFI). This report presents surveillance data for 2017 and 2018. Methods: Specialist nurses screened hospital admissions, emergency department (ED) records, laboratory and other data on a daily basis in seven paediatric tertiary referral hospitals across Australia to identify children with the conditions under surveillance. In 2017 and 2018 these included acute flaccid paralysis (AFP; a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal, and invasive Group A streptococcus diseases. An additional social research component was added to evaluate parental attitudes to vaccination. Results: PAEDS captured 1,580 and 925 cases for 2017 and 2018, respectively, across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach the World Health Organization reporting targets; identification of a third human parechovirus outbreak among other infectious diseases linked to ACE; demonstration of variable influenza activity between 2017 and 2018, with vaccine effectiveness (VE) analysis demonstrating that the protection offered through vaccination is season-dependent. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers remained unchanged, with vaccine uptake found to be suboptimal among eligible children under the NIP. Enhanced pertussis surveillance continues to capture controls for VE estimation. Surveillance for invasive meningococcal disease showed predominance for serotype B at 57% over 2 years among 77 cases where serotyping was available, and surveillance for invasive group A streptococcus captured severe disease in children. Conclusion: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Respiratory syncytial virus-associated hospitalisations in Australia, 2006-2015.

OBJECTIVE: To estimate rates of respiratory syncytial virus (RSV)-associated hospitalisation across the age spectrum, and to identify groups at particular risk of serious RSV-associated disease. DESIGN, SETTING AND PARTICIPANTS: Retrospective review of National Hospital Morbidity Database data for all RSV-associated hospitalisations in Australia, 2006-2015. MAIN OUTCOMES AND MEASURES: RSV-coded hospitalisation rates by age, sex, Indigenous status, jurisdiction, and seasonality (month and year); hospital length of stay; in-hospital deaths. RESULTS: During 2006-2015, there were 63 814 hospitalisations with an RSV-specific principal diagnostic code; 60 551 (94.9%) were of children under 5 years of age. The hospitalisation rate for children under 5 years was 418 per 100 000 population; for children under 6 months of age it was 2224 per 100 000 population; the highest rate was for infants aged 0-2 months (2778 per 100 000 population). RSV-coded hospitalisation rates were higher for adults aged 65 or more than for people aged 5-64 years (incidence rate ratio [IRR], 6.6; 95% CI, 6.2-7.1), and were also higher for Indigenous Australians than other Australians (IRR, 3.3; 95% CI, 3.2-3.5). A total of 138 in-hospital deaths were recorded, including 82 of adults aged 65 years or more (59%). CONCLUSIONS: Prevention strategies targeting infants, such as maternal or early infant vaccination, would probably have the greatest impact in reducing RSV disease rates. Further characterisation of RSV disease epidemiology, particularly in older adults and Indigenous Australians, is needed to inform health care strategies.

Paediatric Active Enhanced Disease Surveillance (PAEDS) annual report 2016: Prospective hospital-based surveillance for serious paediatric conditions

Introduction: The Paediatric Active Enhanced Disease Surveillance (PAEDS) network is a hospital-based active surveillance system employing prospective case ascertainment for selected serious childhood conditions, particularly vaccine preventable diseases and potential adverse events following immunisation (AEFI). PAEDS data is used to better understand these conditions, inform policy and practice under the National Immunisation Program, and enable rapid public health responses for certain conditions of public health importance. PAEDS enhances data available from other Australian surveillance systems by providing prospective, detailed clinical and laboratory information on children with selected conditions. This is the third annual PAEDS report, and presents surveillance data for 2016. Methods: Specialist nurses screened hospital admissions, emergency department records, laboratory and other data, on a daily basis in 5 paediatric tertiary referral hospitals in New South Wales, Victoria, South Australia, Western Australia and Queensland to identify children with the conditions under surveillance. Retrospective data on some conditions was also captured by an additional hospital in the Northern Territory. Standardised protocols and case definitions were used across all sites. Conditions under surveillance in 2016 included acute flaccid paralysis (AFP) (a syndrome associated with poliovirus infection), acute childhood encephalitis (ACE), influenza, intussusception (IS; a potential AEFI with rotavirus vaccines), pertussis, varicella-zoster virus infection (varicella and herpes zoster), invasive meningococcal and invasive Group A streptococcus diseases. Most protocols restrict eligibility to hospitalisations; Emergency Department (ED) only presentations are also included for some conditions. Results: In 2016, there were 673 cases identified across all conditions under surveillance. Key outcomes of PAEDS included: contribution to national AFP surveillance to reach World Health Organization (WHO) reporting targets; identification of the leading infectious causes of acute encephalitis which included human parechovirus, influenza, enteroviruses, Mycoplasma pneumoniae, and bacterial meningo-encephalitis; demonstration of high influenza activity with vaccine effectiveness (VE) analysis demonstrating some protection offered through vaccination. All IS cases associated with vaccine receipt were reported to the relevant state health department. Varicella and herpes zoster case numbers increased from previous years associated with suboptimal vaccination in up to 40% of cases identified. Pertussis surveillance continued in 2016 with the addition of test negative controls captured for estimating vaccine effectiveness. Surveillance for invasive meningococcal disease showed predominance for serotype B in absence of immunisation, and new invasive group A streptococcus surveillance captured severe disease in children. Conclusions: PAEDS continues to provide unique policy-relevant data on serious paediatric conditions using hospital-based sentinel surveillance.

Evaluation of national guidelines for bronchiolitis: AGREEments and controversies.

AIM: Bronchiolitis is a common respiratory illness and is a leading cause of hospitalisation in infancy. We aimed to appraise three recent national bronchiolitis guidelines produced by the Australasian Paediatric Research in Emergency Departments International Collaborative, the National Institute for Health and Care Excellence in the UK and the American Academy of Pediatrics. METHODS: A group of final-year medical students and one senior clinician used the AGREE II tool to appraise each guideline in two stages. First, two students appraised each guideline independently and presented their results. Second, two self-selected students met with the senior clinicians to review all scores to ensure completeness of the appraisal and consistency of AGREE II application. RESULTS: The guidelines scored well overall, with particular strengths in the domains of clarity of presentation, scope and purpose and rigour of development. Comparison of the recommendations across each guideline demonstrated a high degree of consistency. Notable differences included recommendations for the role of palivizumab in prevention of bronchiolitis, the use of continuous pulse oximetry monitoring in the hospitalised patient and the value of respiratory virus testing. CONCLUSIONS: Our appraisal of bronchiolitis guidelines from three high-income countries demonstrated that they were of high quality, with substantial areas of agreement. Most aspects of clinical practice should be uniform for this common paediatric condition. Areas of guideline weakness were in the domains of applicability and editorial independence. We identified three areas of controversy where further research is needed to support stronger evidence-based recommendations.