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Background Pregnancy and early infancy are increased risk periods for severe adverse effects of respiratory infections. Aboriginal and/or Torres Strait Islander (respectfully referred to as First Nations) women and children in Australia bear a disproportionately higher burden of respiratory diseases compared to non-Indigenous women and infants. Influenza vaccines and whooping cough (pertussis) vaccines are recommended and free in every Australian pregnancy to combat these infections. We aimed to assess the equity of influenza and/or pertussis vaccination in pregnancy for three priority groups in Australia: First Nations women; women from culturally and linguistically diverse (CALD) backgrounds; and women living in remote areas or socio-economic disadvantage. Methods We conducted individual record linkage of Perinatal Data Collections with immunisation registers/databases between 2012 and 2017. Analysis included generalised linear mixed model, log-binomial regression with a random intercept for the unique maternal identifier to account for clustering, presented as prevalence ratios (PR) and 95% compatibility intervals (95%CI). Results There were 445,590 individual women in the final cohort. Compared with other Australian women (n = 322,848), First Nations women (n = 29,181) were less likely to have received both recommended antenatal vaccines (PR 0.69, 95% CI 0.67–0.71) whereas women from CALD backgrounds (n = 93,561) were more likely to have (PR 1.16, 95% CI 1.10–1.13). Women living in remote areas were less likely to have received both vaccines (PR 0.75, 95% CI 0.72–0.78), and women living in the highest areas of advantage were more likely to have received both vaccines (PR 1.44, 95% CI 1.40–1.48). Conclusions Compared to other groups, First Nations Australian families, those living in remote areas and/or families from lower socio-economic backgrounds did not receive recommended vaccinations during pregnancy that are the benchmark of equitable healthcare. Addressing these barriers must remain a core priority for Australian health care systems and vaccine providers. An extension of this cohort is necessary to reassess these study findings.

Treatment for pulmonary exacerbations of cystic fibrosis (CF) can produce a range of positive and negative outcomes. Understanding which of these outcomes are achievable and desirable to people affected by disease is critical to agreeing to goals of therapy and determining endpoints for trials. The relative importance of outcomes resulting from treatment of these episodes are not reported. We aimed to (i) quantify the relative importance of outcomes resulting from treatment for pulmonary exacerbations and (ii) develop patient and proxy carer-reported weighted outcome measures for use in adults and children, respectively.A discrete choice experiment (DCE) survey was conducted. Participants were asked to make a series of hypothetical decisions about treatment for pulmonary exacerbations to assess how they make trade-offs between different attributes of health. Data were analysed using a conditional logistic regression model. The correlation coefficients from these data were rescaled to enable generation of a composite health outcome score between 0 and 100 (worst to best health state).362 individuals participated (167 people with CF and 195 carers); of these, 206 completed the survey (56.9%). Most participants were female and resided in Australia. Difficult/painful breathing had the greatest impact on the preferred health state amongst people with CF and carers alike. Avoidance of gastrointestinal problems also heavily influenced decision-making.These data should be considered when making treatment decisions and determining endpoints for trials. Further research is recommended to quantify the preferences of children and to determine whether these align with those of their carer(s).

Children with cochlear implants are at increased risk of invasive pneumococcal disease, with national and international guidelines recommending additional pneumococcal vaccines for these children. This study aimed to examine the pneumococcal immunization status and rate of invasive pneumococcal disease in children with cochlear implants at a tertiary paediatric hospital over a 12-year period. Additionally, the impacts of vaccination reminders and a dedicated immunization clinic on pneumococcal vaccination rates were assessed. This quality improvement study included 200 children who had received a cochlear implant through the Children's Hearing Implant Program at a tertiary paediatric hospital servicing the state of Western Australia. The majority of children (88%) were not up to date with additionally recommended pneumococcal vaccinations. Over the 12-year study period, 2% of children developed invasive pneumococcal disease associated with cochlear implant infections. Generic and personalized electronic immunization reminders improved pneumococcal vaccine up-take in this paediatric cochlear implant setting from 12% (19/153) at baseline to 49% (75/153, p 0.0001) post implementation. The value of a nurse-led dedicated immunization clinic was also demonstrated with all children (42/42, 100%) up to date with Prevenar13 and the majority (34/42, 81%) up to date with Pneumovax23 post initiation of this referral pathway. These data support the expansion of this model to other medically-at-risk paediatric groups that have been highlighted consistently to be under-vaccinated.

The role Staphylococcus aureus antimicrobial resistance genes and toxins play in disease severity, management and outcome in childhood is an emerging field requiring further exploration.A prospective multisite study of Australian and New Zealand children hospitalised with S. aureus bacteraemia (SAB) occurred over 24 months (2017-2018). Whole genome sequencing (WGS) data were paired with clinical information from the ISAIAH cohort.353 SAB isolates were sequenced; 85% methicillin-susceptible S. aureus ([MSSA], 301/353) and 15% methicillin-resistant S. aureus ([MRSA], 52/353). There were 92 sequence types (STs), most commonly ST5 (18%) and ST30 (8%), grouped into 23 clonal complexes (CCs), most frequently CC5 (21%) and CC30 (12%). MSSA comprised the majority of healthcare-associated SAB (87%, 109/125), with principal clones CC15 (48%, 11/21) and CC8 (33%, 7/21). Panton-Valentine leukocidin (PVL)-positive SAB occurred in 22% (76/353); predominantly MSSA (59%, 45/76), community-onset (92%, 70/76) infections. For community-onset SAB, the only microbiological independent predictor of poor outcomes was PVL positivity (aOR 2.6 [CI 1.0-6.2]).From this WGS paediatric SAB data, we demonstrate the previously under-recognized role MSSA has in harbouring genetic virulence and causing healthcare-associated infections. PVL positivity was the only molecular independent predictor of poor outcomes in children. These findings underscore the need for further research to define the potential implications PVL-producing strains may have on approaches to S. aureus clinical management.

To describe the clinical epidemiology of children receiving cochlear implants, as well as the management and outcomes of cochlear implant infections and adherence to infection prevention measures.A retrospective observational study was conducted in children ≤18 years who received cochlear implants in Western Australia's tertiary paediatric hospital. Information was obtained from medical and laboratory records regarding demographics, indication for implant, implant infection and preoperative Staphylococcus aureus screening/decolonisation. Immunisation history was examined using the Australian Immunisation Register.Overall, 118 children received cochlear implants, with 158 devices inserted (599 cochlear implant insertion-years). An implant infection rate of 3.8% (6/158) was identified during the study period (four pneumococcal and two community-acquired methicillin resistant S. aureus infections). All required surgical management, with an overall median duration of antibiotic therapy of 37 days (interquartile range (IQR) 29-48) and median length of stay of 8 days (IQR 8-9.5). All devices were retained and there were no relapses or deaths. Half of the children who developed cochlear implant infections (50%, 3/6) were up-to-date with additional pneumococcal vaccinations and no children (0%, 0/118) received S. aureus screening/decolonisation before implant insertion.Favourable outcomes were achieved with cochlear implant retention; however, the treatment was burdensome for families. We demonstrate significant scope to improve adherence to existing infection prevention strategies and provide direction for optimising preventative measures in the future. These include ensuring parental education, additional pneumococcal vaccinations and S. aureus decolonisation which are delivered as an infection prevention bundle to the growing population of infants receiving cochlear implants.

Invasive pulmonary aspergillosis remains a major cause of morbidity and mortality for immunocompromised children, particularly for patients with acute leukaemia and those undergoing haematopoietic stem cell transplantation. Timely diagnosis, using a combination of computed tomography (CT) imaging and microbiological testing, is key to improve prognosis, yet there are inherent challenges in this process. For CT imaging, changes in children are generally less specific than those reported in adults and recent data are limited. Respiratory sampling by either bronchoalveolar lavage or lung biopsy is recommended but is not always feasible in children, and serum biomarkers, including galactomannan, have important limitations. In this review we summarise the current paediatric data on available diagnostic tests for IPA and highlight key emerging diagnostic modalities with potential for future use.

Background Pneumococcal conjugate vaccines (PCV) reduced the risk of respiratory syncytial virus (RSV) in a randomized clinical trial. We aimed to assess the real-world effectiveness of PCV on RSV-hospitalizations among Western Australian infants. Methods We conducted a population-based cohort study of births during 2000–2012, using probabilistically linked individual-level immunization, hospitalization, respiratory microbiology testing, and perinatal data. We performed Cox proportional hazard models with time-varying exposure (receipt of infant PCV doses) against the first RSV-confirmed hospitalization 0–12 months adjusted for perinatal and sociodemographic factors. Results From 360 994 children, 3-dose PCV coverage in Aboriginal infants ranged from 29% to 51% in 2001–2004 when PCV was funded for Aboriginal children only. Following universal funding in 2005, coverage increased to 85% for Aboriginal and 73% for non-Aboriginal infants. RSV-hospitalization rates were highest in young infants aged 0–5 months (22.5/1000 child-years) and >2 times higher in Aboriginal infants than in non-Aboriginal infants. Receipt of ≥3 PCV doses in the universal funded period was associated with a 30% reduction in RSV-hospitalization in Aboriginal infants (adjusted hazard ratio, aHR 0.70 [95% confidence interval, CI 0.46–1.06]) and 21% reduction in non-Aboriginal infants (aHR 0.79 [95% CI 0.63–0.99]) compared with unvaccinated infants. Conclusions Prior to the introduction of RSV vaccines, our study suggests that universal childhood PCV vaccination may result in a reduction in severe RSV infections in children and may be important for countries that are yet to consider PCV programs.

Background The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. Methods The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer’s Comirnaty, Moderna’s Spikevax or Novavax’s Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. Discussion PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

Background While most Australian children are vaccinated, delays in vaccination can put them at risk from preventable infections. Widespread mobile phone ownership in Australia could allow automated short message service (SMS) reminders to be used as a low-cost strategy to effectively ‘nudge’ parents towards vaccinating their children on time. Methods AuTOMATIC is an adaptive randomised trial which aims to both evaluate and optimise the use of SMS reminders for improving the timely vaccination of children at primary care clinics across Australia. The trial will utilise high levels of digital automation to effect, including eligibility assessment, randomisation, delivery of intervention, data extraction and analysis, thereby allowing healthcare-embedded trial delivery. Up to 10,000 parents attending participating primary care clinics will be randomised to one of 12 different active SMS vaccine reminder content and timing arms or usual practice only (no SMS reminder). The primary outcome is vaccine receipt within 28 days of the scheduled date for the index vaccine (the first scheduled vaccine after randomisation). Secondary analyses will assess receipt and timeliness for all vaccine occasions in all children. Regular scheduled analyses will be performed using Bayesian inference and pre-specified trial decision rules, enabling response adaptive randomisation, suspension of any poorly performing arms and early stopping if a single best message is identified. Discussion This study will aim to optimise SMS reminders for childhood vaccination in primary care clinics, directly comparing alternative message framing and message timing. We anticipate that the trial will be an exemplar in using Bayesian adaptive methodology to assess a readily implementable strategy in a wide population, capable of delivery due to the levels of digital automation. Methods and findings from this study will help to inform strategies for implementing reminders and embedding analytics in primary health care settings. Trial registration ANZCTR: ACTRN12618000789268.

To describe and explore the relationship between weather and the unusual 2020 bronchiolitis season in Western Australia during the COVID-19 pandemic.Correlation of meteorological data and presentations of infants with bronchiolitis through the ED of Perth Children's Hospital.The 2020 bronchiolitis epidemic showed a reversal of the usual seasonal pattern. There were no weather events to account for this phenomenon.The bronchiolitis outbreak showed no relationship to local weather patterns. State-mandated COVID-19 public health measures appear as the likely rationale.

We assessed the utility of routine viral surveillance for cytomegalovirus, Epstein-Barr virus and human adenovirus in children16 years, undergoing autologous stem cell transplantation (ASCT) at a single centre over a 10-year period. A total of 85 ASCT were performed in 65 patients. Routine viral surveillance resulted in a high number of tests performed (median 20 tests per ASCT), without any clinically significant viral detections. These data support the limited clinical utility of routine viral surveillance in children undergoing ASCT. Adopting a clinically driven approach for viral testing is likely to be both cost-effective and safe.

Antimicrobials are the most commonly prescribed drug class in children. Overuse through inappropriate prescribing is a key driver of antimicrobial resistance and is recognized as one of the top 10 threats to global health by the World Health Organization.A prospective observational cohort study was performed following implementation of a multifaceted Antimicrobial Stewardship (AMS) program (January 2014 to December 2020). Data were collected on AMS and "handshake" ward rounds from patient information sources and directly from clinicians responsible for patient care. Primary outcomes include appropriateness of therapy (drug, dose, antimicrobial spectrum, duration and route), compliance with prescribing guidelines, antimicrobial expenditure, use of high-priority antimicrobials and duration of hospitalization. We compared outcomes across 3 time periods; January 2014-December 2015, January 2016-December 2017 and January 2018-December 2020.The appropriateness of individual antimicrobial orders improved across the study periods from 6111/7040 (79.4%) in the first 2 years following implementation of the AMS program to 17,819/19,229 (92.3%) in the latter period. Guideline compliance increased from 5426/7700 (70.5%) to 17,822/19,316 (92.3%). A reduction in overall antimicrobial expenditure (34% reduction, equivalent to $12.52 per bed day) and a decrease in antifungal expenditure (37% reduction, equivalent to $5.56 per bed day) was observed across the time periods.This study quantifies a comprehensive pediatric AMS program's sustained impact on reducing inappropriate antimicrobial use and expenditure and improving compliance with guidelines. The effectiveness of these interventions has been demonstrated and should be considered by institutions seeking to improve rational antimicrobial use in children.

Culturally and Linguistically Diverse (CALD) groups within high-income countries are at risk of being left behind by the COVID-19 vaccination rollout. They face both access and attitudinal barriers, including low trust in government and health authorities.To explore perceptions and attitudes towards COVID-19 vaccination, as well as facilitators, barriers and strategies to promote uptake among CALD residents of Western Australia (WA), where there were almost no COVID-19 cases for 2 years.Perth, WA's capital, was chosen as the state's study site because most of the state's CALD population lives there. Eleven semistructured in-depth interviews and three focus groups (with 37 participants) were conducted with CALD residents between August and October 2021. Thematic analysis was conducted, informed by the 'Capability', 'Opportunity', 'Motivation', 'Behaviour' model.CALD participants faced barriers including a lack of knowledge about COVID-19 and the vaccines, low self-rated English proficiency and education levels, misinformation, passive government communication strategies and limited access to vaccine clinics/providers. They were, however, motivated to vaccinate by the imminent opening of state and international borders, trust in government and healthcare authorities, travel intentions and the desire to protect themselves and others.Despite high levels of trust and significant desire for vaccines among CALD communities in Perth, current strategies were not meeting their needs and the community remains at risk from COVID-19. Tailored intervention strategies are required to provide knowledge, address misinformation and facilitate access to ensure uptake of COVID-19 vaccines-including for additional doses-amongst CALD communities. Governments should work with trusted CALD community members to disseminate tailored COVID-19 vaccine information and adequately translated resources.The Wesfarmers Centre of Vaccines and Infectious Diseases Community Reference Group at Telethon Kids Institute consulted on this project in September 2020; Ishar Multicultural Women's Health Services consulted on and facilitated the focus groups.

Background Diagnosing urinary tract infections (UTIs) in children in the emergency department (ED) is challenging due to the variable clinical presentations and difficulties in obtaining a urine sample free from contamination. Clinicians need to weigh a range of observations to make timely diagnostic and management decisions, a difficult task to achieve without support due to the complex interactions among relevant factors. Directed acyclic graphs (DAG) and causal Bayesian networks (BN) offer a way to explicitly outline the underlying disease, contamination and diagnostic processes, and to further make quantitative inference on the event of interest thus serving as a tool for decision support. Methods We prospectively collected data on children present to ED with suspected UTIs. Through knowledge elicitation workshops and one-on-one meetings, a DAG was co-developed with clinical domain experts (the Expert DAG) to describe the causal relationships among variables relevant to paediatric UTIs. The Expert DAG was combined with prospective data and further domain knowledge to inform the development of an application-oriented BN (the Applied BN), designed to support the diagnosis of UTI. We assessed the performance of the Applied BN using quantitative and qualitative methods. Results We summarised patient background, clinical and laboratory characteristics of 431 episodes of suspected UTIs enrolled from May 2019 to November 2020. The Expert DAG was presented with a narrative description, elucidating how infection, specimen contamination and management pathways causally interact to form the complex picture of paediatric UTIs. Parameterised using prospective data and expert-elicited parameters, the Applied BN achieved an excellent and stable performance in predicting Escherichia coli culture results, with a mean area under the receiver operating characteristic curve of 0.86 and a mean log loss of 0.48 based on 10-fold cross-validation. The BN predictions were reviewed via a validation workshop, and we illustrate how they can be presented for decision support using three hypothetical clinical scenarios. Conclusion Causal BNs created from both expert knowledge and data can integrate case-specific information to provide individual decision support during the diagnosis of paediatric UTIs in ED. The model aids the interpretation of culture results and the diagnosis of UTIs, promising the prospect of improved patient care and judicious use of antibiotics.

We describe contemporary antifungal use in neonates, with point-prevalence survey data from the National Antimicrobial Prescribing Survey across Australian hospitals from 2014 to 2018. There were 247 antifungal prescriptions in 243 neonates in 20 hospitals, median age six days (range 0–27 days). In 219/247 prescriptions (89%) antifungals were prescribed as prophylaxis. Topical (oral) nystatin was the most frequently prescribed in 233/247 prescriptions (94%), followed by fluconazole 11/227 (4%), with substantial variation in dosing for both. Two of 243 neonates (0.8%) had invasive fungal infection. Nystatin use dominates current antifungal prescribing for Australian neonates, in contrast to other countries, and invasive fungal infection is rare. Lay summary Novel nationwide surveillance found newborn infants in Australian hospitals commonly receive antifungal medications, mostly oral nystatin. This is given mainly to prevent rather than treat infection, which is rare. There is substantial unexplained variation in dosing of antifungal drugs nationally.

Background Staphylococcus aureus is a common cause of bacteremia, yet the epidemiology and predictors of poor outcome remain inadequately defined in childhood. Methods ISAIAH (Invasive Staphylococcus aureus Infections and Hospitalizations in children) is a prospective, cross-sectional study of S. aureus bacteremia (SAB) in children hospitalized in Australia and New Zealand over 24 months (2017–2018). Results Overall, 552 SABs were identified (incidence 4.4/100 000/year). Indigenous children, those from lower socioeconomic areas and neonates were overrepresented. Although 90-day mortality was infrequent, one-third experienced the composite of: length of stay >30 days (26%), intensive care unit admission (20%), relapse (4%), or death (3%). Predictors of mortality included prematurity (adjusted odds ratio [aOR],16.8; 95% confidence interval [CI], 1.6–296.9), multifocal infection (aOR, 22.6; CI, 1.4–498.5), necrotizing pneumonia (aOR, 38.9; CI, 1.7–1754.6), multiorgan dysfunction (aOR, 26.5; CI, 4.1–268.8), and empiric vancomycin (aOR, 15.7; CI, 1.6–434.4); while infectious diseases (ID) consultation (aOR, 0.07; CI .004–.9) was protective. Neither MRSA nor vancomycin trough targets impacted survival; however, empiric vancomycin was associated with nephrotoxicity (OR, 3.1; 95% CI 1.3–8.1). Conclusions High SAB incidence was demonstrated and for the first time in a pediatric setting, necrotizing pneumonia and multifocal infection were predictors of mortality, while ID consultation was protective. The need to reevaluate pediatric vancomycin trough targets and limit unnecessary empiric vancomycin exposure to reduce poor outcomes and nephrotoxicity is highlighted. One in 3 children experienced considerable SAB morbidity; therefore, pediatric inclusion in future SAB comparator trials is paramount to improve outcomes.

Streptococcus pneumoniae (the pneumococcus) is a human pathogen of global importance, classified into serotypes based on the type of capsular polysaccharide produced. Serotyping of pneumococci is essential for disease surveillance and vaccine impact measurement. However, the accuracy of serotyping methods can be affected by previously undiscovered variants. Previous studies have identified variants of serotype 14, a highly invasive serotype included in all licensed vaccine formulations. However, the potential of these variants to influence serotyping accuracy and evade vaccine-induced protection has not been investigated. In this study, we screened 1,386 nasopharyngeal swabs from children hospitalized with acute respiratory infection in Papua New Guinea for pneumococci. Swabs containing pneumococci (n = 1,226) were serotyped by microarray to identify pneumococci with a divergent serotype 14 capsule locus. Three serotype 14 variants ('14-like') were isolated and characterized further. The serotyping results of these isolates using molecular methods varied depending on the method, with 3/3 typing as nontypeable (PneumoCaT), 3/3 typing as serotype 14 (seroBA), and 2/3 typing as serotype 14 (SeroCall and quantitative PCR). All three isolates were nontypeable by phenotypic methods (Quellung and latex agglutination), indicating the absence of capsule. Illumina and nanopore sequencing were employed to examine their capsule loci and revealed unique mutations. Lastly, when incubated with sera from vaccinated individuals, the 14-like isolates evaded serotype-specific opsonophagocytic killing. Our study highlights the need for phenotypic testing to validate serotyping data derived from molecular methods. The convergent evolution of capsule loss underscores the importance of studying pneumococcal population biology to monitor the emergence of pneumococci capable of vaccine escape, globally. IMPORTANCE Pneumococcus is a pathogen of major public health importance. Current vaccines have limited valency, targeting a subset (up to 20) of the more than 100 capsule types (serotypes). Precise serotyping methods are therefore essential to avoid mistyping, which can reduce the accuracy of data used to inform decisions around vaccine introduction and/or maintenance of national vaccination programs. In this study, we examine a variant of serotype 14 (14-like), a virulent serotype present in all currently licensed vaccine formulations. Although these 14-like pneumococci no longer produce a serotype 14 capsule, widely used molecular methods can mistype them as serotype 14. Importantly, we show that 14-like pneumococci can evade opsonophagocytic killing mediated by vaccination. Despite the high accuracy of molecular methods for serotyping, our study reemphasizes their limitations. This is particularly relevant in situations where nonvaccine type pneumococci (e.g., the 14-likes in this study) could potentially be misidentified as a vaccine type (e.g., serotype 14).

Acute flaccid paralysis (AFP) surveillance continues globally as part of the World Health Organization's goal to eradicate poliomyelitis. The Australian Paediatric Surveillance Unit (APSU), Paediatric Active Enhanced Disease Surveillance (PAEDS) network, and National Enterovirus Reference Laboratory (NERL) collaborate in acute flaccid paralysis surveillance in Australia, capturing and reviewing cases of AFP for all etiologies in order to exclude poliovirus. . We aimed to describe the AFP epidemiology in childhood over an eleven year period.Data were reported nationally by paediatricians via prospective APSU surveillance, PAEDS surveillance nurses at five tertiary paediatric hospitals and NERL from 2007 to 2017. Children aged 0-15 years with AFP were included. We combined APSU, PAEDS and NERL datasets, analysed epidemiological trends and described clinical features and investigations for major diagnoses.Of 590 AFP-compatible cases, 49% were male; 47% were aged 0-4 years, 9% aged1 year.. Annual incidence of AFP was 1.3 cases per 100,000 children aged15 years. Lower limb paralysis was the most frequent presenting symptom. The most frequent diagnoses were Guillain-Barre syndrome (GBS; 36%), transverse myelitis (TM; 17%) and acute disseminated encephalomyelitis (ADEM; 15%). No secular trend was seen in frequency of AFP cases nor amongst major diagnoses. Seasonality was observed with ADEM occurring more frequently in winter. We observed periods of increased AFP frequency in 2013 and 2016, coinciding with increased reporting of non-polio anterior horn cell disease (AHCD) and detection of non-polio enterovirus (NPEV).Estimated incidence of GBS, ADEM and TM in Australian children were comparable with international rates. There was stable incidence of AFP in Australian children between 2007 and 2017. GBS, ADEM and TM are the major causes of AFP. We observed clustering of cases associated with NPEV that emphasises a need for ongoing vigilance in surveillance given continue emerging infectious disease threats.

AIM Rapid blood culture pathogen identification facilitated by matrix-assisted laser desorption ionisation time-of-flight and GeneXpert has the potential to improve antibiotic prescribing. This study investigates the impact of these rapid diagnostics on the timeliness of effective and optimal antibiotic prescribing in paediatric patients with bacteraemia. METHODS A single centre retrospective cohort study was performed comparing paediatric bacteraemia cases pre- and post-rapid diagnostic implementation. Primary outcomes were the proportion of cases receiving, and median time to administration of effective and optimal antibiotics from blood culture collection. Secondary outcomes included hospital length of stay, intensive care unit admissions, and all-cause mortality. RESULTS A total of 255 bacteraemia cases were subject to final data analysis, 129 in the control cohort (pre-implementation of rapid diagnostics) and 126 in the rapid diagnostics cohort. The median time to effective (2.3 vs. 1.8 h, P = 0.20) and optimal therapy (44.4 vs. 39.1 h, P = 0.66) did not differ significantly between the cohorts. There was also no significant difference found in the number of cases reaching effective (120 vs. 116, P = 0.77) and optimal therapy (66 vs. 62, P = 0.76), length of stay (7 vs. 9 days), all-cause mortality (1.6 vs. 1.6%) and number of intensive care unit admissions (20 vs. 15). CONCLUSION The implementation of rapid diagnostics, when used in isolation, resulted in no improvement in antibiotic prescribing or patient clinical outcomes. To be effective, rapid diagnostics must be coupled with active real-time antimicrobial stewardship promotion, de-escalation or modification based on early laboratory results.

Aim To examine rates and predictors of 7-day readmission in infants hospitalised before 3 months of age with infectious and non-infectious conditions. Methods Retrospective population-based data-linkage study of 121 854 infants from a 5-year metropolitan birth cohort (2008-2012). Cox proportional hazard models were used to examine associations between infant and maternal factors with 7-day readmission. Results A total of 11 669 (9.6%) infants were hospitalised at least once by 3 months of age (median 23 days old, 56% male) with 12 602 total index hospitalisations. Infection-related conditions accounted for 29.4% (n = 3705). Readmission within 7 days occurred after 4.8% of all index hospitalisations and 5.4% of infection-related hospitalisations. Age ≤21 days was the strongest readmission risk factor (hazard ratio 7.7 (95% confidence interval 4.7-12.7) compared to infants 61-90 days old). Other risk factors included shorter index hospitalisations, younger maternal age and multi-gravidity. Conclusion Hospitalisations and readmissions occur for many young infants. Risk factors for readmission should inform risk-based management guidelines.

Background There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations in people with cystic fibrosis (CF). Outcomes used for evaluation should be meaningful; that is, they should capture how people feel, function or survive and be acknowledged as important to people with CF, or should be reliable surrogates of those outcomes. We aimed to summarise the outcomes and corresponding endpoints which have been reported in studies of pulmonary exacerbations, and to identify those which are most likely to be meaningful. Methods A PROSPERO registered systematic review (CRD42020151785) was conducted in Medline, Embase and Cochrane from inception until July 2020. Registered trials were also included. Results 144 studies met the inclusion criteria. A wide range of outcomes and corresponding endpoints were reported. Death, QoL and many patient-reported outcomes are likely to be meaningful as they directly capture how people feel, function or survive. Forced expiratory volume in 1-second [FEV1] is a validated surrogate of risk of death and reduced QoL. The extent of structural lung disease has also been correlated with lung function, pulmonary exacerbations and risk of death. Since no evidence of a correlation between airway microbiology or biomarkers with clinically meaningful outcomes was found, the value of these as surrogates was unclear. Conclusions Death, QoL, patient-reported outcomes, FEV1, and structural lung changes were identified as outcomes that are most likely to be meaningful. Development of a core outcome set in collaboration with stakeholders including people with CF is recommended.

Aim: To identify barriers to influenza vaccination of children hospitalised for acute respiratory illness in Australia. Methods: A total of 595 parents of children hospitalised with acute respiratory illness across five tertiary hospitals in 2019 participated in an online survey. Multivariate logistic regression identified factors most strongly associated with influenza vaccination barriers. Results: Odds of influenza vaccination were lower with lack of health-care provider (HCP) recommendation (adjusted odds ratio (aOR) 0.18; 95% confidence interval (CI): 0.08–0.38); if parents had difficulties (aOR 0.19; 95% CI: 0.08–0.47) or were ‘neutral’ (aOR 0.23; 95% CI: 0.06–0.82) in remembering to make an appointment; and if parents had difficulties (aOR 0.21; 95% CI: 0.07–0.62) or were ‘neutral’ (aOR 0.24; 95% CI: 0.07–0.79) regarding getting an appointment for vaccination. Odds were also lower if parents did not believe (aOR 0.27; 95% CI: 0.08–0.90) or were ‘neutral’ (aOR 0.15; 95% CI: 0.04–0.49) regarding whether the people most important to them would have their child/ren vaccinated against influenza. Children had lower odds of vaccination if parents did not support (aOR 0.09; 95% CI: 0.01–0.82) or were ambivalent (aOR 0.09; 95% CI: 0.01–0.56) in their support for influenza vaccination. Finally, lack of history of influenza vaccination of child (aOR 0.38; 95% CI: 0.18–0.81) and respondent (aOR 0.25; 95% CI: 0.11–0.56) were associated with lack of receipt of influenza vaccine before admission for acute respiratory infection. Conclusions: Assisting parents in remembering and accessing influenza vaccination and encouraging health-care providers to recommend vaccination may increase uptake.

Public health measures targeting coronavirus disease 2019 have potential to impact transmission of other respiratory viruses. We found 98.0% and 99.4% reductions in respiratory syncytial virus and influenza detections, respectively, in Western Australian children through winter 2020 despite schools reopening. Border closures have likely been important in limiting external introductions.

Rationale: Respiratory syncytial virus (RSV) bronchiolitis causes significant infant mortality. Bronchiolitis is characterized by airway epithelial cell (AEC) death; however, the mode of death remains unknown. Objectives: To determine whether necroptosis contributes to RSV b r onchiolitis pathogenesis via HMGB1 (high mobility group box 1) release. Methods: Nasopharyngeal samples were collected from children presenting to the hospital with acute respiratory infection. Primary human AECs and neonatal mice were inoculated with RSV and murine Pneumovirus, respectively. Necroptosis was determined via viability assays and immunohistochemistry for RIPK1 (receptor-interacting protein kinase-1), MLKL (mixed lineage kinase domain-like pseudokinase) protein, and caspase-3. Necroptosis was blocked using pharmacological inhibitors and RIPK1 kinase-dead knockin mice. Measurements and Main Results: HMGB1 levels were elevated in nasopharyngeal samples of children with acute RSV infection. RSV-induced epithelial cell death was associated with increased phosphorylated RIPK1 and phosphorylated MLKL but not active caspase-3 expression. Inhibition of RIPK1 or MLKL attenuated RSV-induced HMGBI translocation and release, and lowered viral load. MLKL inhibition increased active caspase-3 expression in a caspase-8/9-dependent manner. In susceptible mice, Pneumovirus infection upregulated RIPK1 and MLKL expression in the airway epithelium at 8 to 10 days after infection, coinciding with AEC sloughing, HMGB1 release, and neutrophilic inflammation. Genetic or pharmacological inhibition of RIPK1 or MLKL attenuated these pathologies, lowered viral load, and prevented type 2 inflammation and airway remodeling. Necroptosis inhibition in early life ameliorated asthma progression induced by viral or allergen challenge in later life. Conclusions: Pneumovirus infection induces AEC necroptosis. Inhibition of necroptosis may be a viable strategy to limit the severity of viral bronchiolitis and break its nexus with asthma.

BACKGROUND Post-licensure surveillance studies have shown a small but increased risk of intussusception among infants in the days following rotavirus vaccination (RV). OBJECTIVES We assessed the temporal trends of intussusception-coded hospitalisations before and after the commencement of a universal rotavirus vaccination programme in Western Australia (WA) in 2007. We also assessed the perinatal factors and pathogens associated with these hospitalisations. METHODS Intussusception-coded hospitalisations occurring in a cohort of 367 476 WA-born children (2000-2012) aged

Background There is increasing knowledge of antimicrobial usage in children yet limited availability of nationally representative paediatric-specific data on antimicrobial resistance. Objectives Paediatric data from this national surveillance programme are presented to explore differences between childhood and adult bloodstream infections and antimicrobial resistance surveillance. Methods Using information collected from a prospective coordinated antimicrobial resistance surveillance programme, children ≤18 years and adults >18 years with a positive blood culture for Staphylococcus aureus, Enterococcus spp. or Gram-negative spp. presenting to one of 34 Australian hospitals during 2013–16 were evaluated. Consistent methodologies for key sepsis pathogens were employed and a comparative analysis between children and adults was conducted. Results There are stark contrasts between children and adults in this national antimicrobial resistance (AMR) data set. Notable differences include lower rates of AMR, different clinical and molecular phenotypes and lower mortality amongst children. The burden of Gram-negative resistance is disproportionately experienced in children, with higher odds of death with an ESBL versus non-ESBL bacteraemia in comparison with adults. Conclusions These data support that children are not just ‘little adults’ in the AMR era, and analyses by age group are important to detect differences in antibiotic susceptibility, clinical phenotype and genetic virulence factors. Antimicrobial surveillance incorporated into routine laboratory practice is vital to inform an array of wider applications including antimicrobial guidelines, stewardship and direction for prioritization of novel antimicrobial development.

Encephalitis is most often caused by a variety of infectious agents identified through diagnostic tests utilizing cerebrospinal fluid. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic sequencing of residual clinical samples from multiple tissue types and independent clinical review. Forty-three specimens were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing (‘metatranscriptomics’) to determine the presence and abundance of potential pathogens, and to describe the possible aetiologies of unexplained encephalitis. Using this protocol, we identified five RNA and two DNA viruses associated with human infection from both non-sterile and sterile sites, which were confirmed by PCR. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases. Immune-mediated encephalitis was considered likely in six cases and metatranscriptomics did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasizes the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that non-central-nervous-system sampling in encephalitis clinical guidelines and protocols could improve the diagnostic yield.

Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza during the 2019 influenza season. The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Cases were defined as patients hospitalised at any of the 17 sentinel hospitals with influenza confirmed by nucleic acid detection. Data were also collected on a frequency matched control group of influenza-negative patients admitted with acute respiratory infection. During the period 1 April to 31 October 2019 (the 2019 influenza season), there were 4,154 patients admitted with confirmed influenza to one of 17 FluCAN sentinel hospitals. Of these, 44% were elderly (≥ 65 years), 21% were children (< 16 years), 7.7% were Aboriginal and Torres Strait Islander peoples, 1.7% were pregnant and 73% had chronic comorbidities. Most admissions were due to influenza A infection (85%). Estimated vaccine coverage was 75% in the elderly, 49% in non-elderly adults with medical comorbidities, and 27% in young children (< 5 years). The estimated vaccine effectiveness in the target adult population was 42% (95% confidence interval [95% CI]: 36%, 49%). There were a larger number of hospital admissions detected with confirmed influenza in this national observational surveillance system in 2019 than in 2018.

Pneumonia is a leading cause of childhood mortality withData from two consecutive prospective observational studies (2013-2019) enrolling children60 months presenting with pneumonia were included. Hypoxic pneumonia was defined as oxygen saturations90%. Outcomes included hospitalisation, severe clinical pneumonia and death. 13vPCV status was determined using written records. Logistic regression models were used to estimate the odds ratios of key outcomes by 13vPCV vaccination status adjusted for confounders using inverse probability of treatment weighting.Data from 2067 children (median age; 9 months [IQR: 5-11]) were included. 739 children (36.1%) were hypoxic and 623 (30.4%) hospitalised. Twelve children (0.6% of total cohort) died in hospital. 670 children (32.7%) were fully 13vPCV-vaccinated. 13vPCV vaccination was associated with a 28.7% reduction (95% confidence interval [CI]: 9.9; 43.6%) in hypoxic pneumonia and a 57.4% reduction (38.0; 70.7%) in pneumonia hospitalisation.13vPCV vaccination is effective against hypoxic pneumonia and pneumonia hospitalisation in PNG children. Strategies to improve access to and coverage of 13vPCV in PNG and other similar LMICs are urgently required.Funded by Pfizer Global and the BillMelinda Gates Foundation.

Invasive fungal disease (IFD) remains a common and serious complication in children treated for leukaemia. Antifungal prescription in children with leukaemia presents unique challenges, particularly due to variation in IFD risk between and within leukaemia treatment protocols, drug toxicities and interactions between antifungals and chemotherapeutic agents. With recent advances in the understanding of IFD epidemiology and large clinical trials in adults assessing antifungals for IFD treatment and prophylaxis, together with paediatric clinical and pharmacokinetic studies, there is a growing body of data to inform optimal antifungal use in children. A panel of infectious diseases and haematology-oncology clinicians with expertise in IFD management compiled a list of 10 key clinical questions following development of the 2021 Australia and New Zealand Mycology Antifungal Consensus Guidelines. A focused literature review was conducted to explore available evidence and identify gaps in knowledge to direct future research. With the changing epidemiology of IFD globally, the ongoing evolution of paediatric leukaemia treatment and the increasing availability of novel antifungal agents, advocacy for paediatric clinical studies will remain vital to optimize IFD prevention and treatment in children with leukaemia.

Background Previous Australian studies have shown that delayed vaccination with each of the three primary doses of diphtheria-tetanus-pertussis-containing vaccines (DTP) is up to 50 % in certain subpopulations. We estimated the excess burden of pertussis that might have been prevented if (i) all primary doses and (ii) each dose was given on time. Methods Perinatal, immunization, pertussis notification and death data were probabilistically linked for 1 412 984 infants born in two Australian states in 2000–12. A DTP dose administered >15 days after the recommended age was considered delayed. We used Poisson regression models to compare pertussis notification rates to 1-year of age in infants with ≥1 dose delayed (Aim 1) or any individual dose delayed (Aim 2) versus a propensity weighted counterfactual on-time cohort. Results Of all infants, 42% had ≥1 delayed DTP dose. We estimated that between 39 to 365 days of age, 85 (95% CI: 61–109) cases per 100 000 infants, could have been prevented if all infants with ≥1 delayed dose had received their three doses within the on-time window. Risk of pertussis was higher in the delayed versus the on-time cohort, so crude rates overestimated the excess burden (110 cases per 100 000 infants (95% CI: 95–125)). The estimated dose-specific excess burden per 100 000 infants was 132 for DTP1, 50 for DTP2 and 19 for DTP3. Conclusions We provide robust evidence that improved DTP vaccine timeliness, especially for the first dose, substantially reduces the burden of infant pertussis. Our methodology, using a potential outcomes framework, is applicable to other settings.

ImportanceChildren with chronic medical conditions are at increased risk of severe influenza. Uptake of influenza vaccination in children and adolescents with these identified special risk medical conditions (SRMCs) is suboptimal.ObjectiveTo assess the effectiveness of Flutext-4U, a parent short message service (SMS) reminder nudge intervention, in increasing influenza immunization in children and adolescents with SRMCs.Design, Setting, and ParticipantsThis randomized clinical trial was conducted at a tertiary pediatric hospital in Adelaide, South Australia, from April 15 to September 30, 2021. Children and adolescents aged 6 months to younger than 18 years with SRMCs and a subspecialist outpatient appointment over a 5-month period during the Australian seasonal influenza vaccination season (April-August 2021) were eligible to participate. Follow-up was until September 30, 2021.InterventionsParticipants were randomly assigned (1:1 ratio) to control: clinician nudges (hospital vaccine availability, ease of access, and recommendation from hospital subspecialists) or SMS intervention (control conditions plus an additional SMS reminder nudge to parents), with randomization stratified by age group (14 to Main Outcomes and MeasuresThe primary outcome was influenza vaccination, as confirmed by the Australian Immunisation Register.ResultsA total of 600 participants (intervention group: 298 [49.7%]; mean [SD] age, 11.5 [4.6] years; 162 female participants [54.4%]; control group: 302 [50.3%]; mean [SD] age, 11.4 [4.7] years; 155 female participants [51.3%]) were included. Influenza vaccination was 38.6% (113 of 293) in the SMS intervention group compared with 26.2% (79 of 302) in the control group (adjusted odds ratio [aOR], 1.79; 95% CI, 1.27-2.55; P = .001). Time to vaccine receipt was significantly lower among SMS participants (adjusted hazard ratio, 1.67; 95% CI, 1.25-2.22; P P = .002).Conclusions and RelevanceResults of this randomized clinical trial suggest that an additional SMS reminder nudge for parents delivered in the tertiary care hospital setting to children and adolescents with SMRCs resulted in higher influenza vaccine uptake compared with clinician nudges alone.Trial RegistrationANZCTR Identifier: ACTRN12621000463875

Background Pneumonia remains a leading cause of hospitalization and death among young children worldwide, and the diagnostic challenge of differentiating bacterial from non-bacterial pneumonia is the main driver of antibiotic use for treating pneumonia in children. Causal Bayesian networks (BNs) serve as powerful tools for this problem as they provide clear maps of probabilistic relationships between variables and produce results in an explainable way by incorporating both domain expert knowledge and numerical data. Methods We used domain expert knowledge and data in combination and iteratively, to construct, parameterise and validate a causal BN to predict causative pathogens for childhood pneumonia. Expert knowledge elicitation occurred through a series of group workshops, surveys and one-on-one meetings involving 6-8 experts from diverse domain areas. The model performance was evaluated based on both quantitative metrics and qualitative expert validation. Sensitivity analyses were conducted to investigate how the target output is influenced by varying key assumptions of a particularly high degree of uncertainty around data or domain expert knowledge. Results Designed to apply to a cohort of children with X-ray confirmed pneumonia who presented to a tertiary paediatric hospital in Australia, the resulting BN offers explainable and quantitative predictions on a range of variables of interest, including the diagnosis of bacterial pneumonia, detection of respiratory pathogens in the nasopharynx, and the clinical phenotype of a pneumonia episode. Satisfactory numeric performance has been achieved including an area under the receiver operating characteristic curve of 0.8 in predicting clinically-confirmed bacterial pneumonia with sensitivity 88% and specificity 66% given certain input scenarios (i.e., information that is available and entered into the model) and trade-off preferences (i.e., relative weightings of the consequences of false positive versus false negative predictions). We specifically highlight that a desirable model output threshold for practical use is very dependent upon different input scenarios and trade-off preferences. Three commonly encountered scenarios were presented to demonstrate the potential usefulness of the BN outputs in various clinical pictures. Conclusions To our knowledge, this is the first causal model developed to help determine the causative pathogen for paediatric pneumonia. We have shown how the method works and how it would help decision making on the use of antibiotics, providing insight into how computational model predictions may be translated to actionable decisions in practice. We discussed key next steps including external validation, adaptation and implementation. Our model framework and the methodological approach can be adapted beyond our context to broad respiratory infections and geographical and healthcare settings.

BackgroundPatient-reported outcome measures (PROMs) are recommended for capturing meaningful outcomes in clinical trials. The use of PROMs for children with acute lower respiratory infections (ALRIs) has not been systematically reported. We aimed to identify and characterise patient-reported outcomes and PROMs used in paediatric ALRI studies and summarise their measurement properties.MethodsMedline, Embase and Cochrane were searched (until April 2022). Studies that reported on patient-reported outcome (or measure) use or development and included subjects aged ResultsOf 2793 articles identified, 18 met inclusion criteria, including 12 PROMs. Two disease-specific PROMs were used in settings in which they had been validated. The Canadian Acute Respiratory Illness and Flu Scale was the most frequently used disease-specific PROM (five studies). The EuroQol-Five Dimensions-Youth system was the most frequently used generic PROM (two studies). There was considerable heterogeneity in validation methods. The outcome measures identified in this review lack validation for young children and none involve sufficient content validity for use with First Nations children.ConclusionsThere is an urgent need for PROM development that considers the populations in which the burden of ALRI predominates.

The Australian Technical Advisory Group on Immunisation and New Zealand Ministry of Health recommend all children aged ≥ 5 years receive either of the two mRNA COVID-19 vaccines: Comirnaty (Pfizer), available in both Australia and New Zealand, or Spikevax (Moderna), available in Australia only. Both vaccines are efficacious and safe in the general population, including children. Children and adolescents undergoing treatment for cancer and immunosuppressive therapy for non-malignant haematological conditions are particularly vulnerable, with an increased risk of severe or fatal COVID-19. There remains a paucity of data regarding the immune response to COVID-19 vaccines in immunosuppressed paediatric populations, with data suggestive of reduced immunogenicity of the vaccine in immunocompromised adults.Considering the safety profile of mRNA COVID-19 vaccines and the increased risk of severe COVID-19 in immunocompromised children and adolescents, COVID-19 vaccination is strongly recommended for this at-risk population. We provide a number of recommendations regarding COVID-19 vaccination in this population where immunosuppressive, chemotherapeutic and/or targeted biological agents are used. These include the timing of vaccination in patients undergoing active treatment, management of specific situations where vaccination is contraindicated or recommended under special precautions, and additional vaccination recommendations for severely immunocompromised patients. Finally, we stress the importance of upcoming clinical trials to identify the safest and most efficacious vaccination regimen for this population.This consensus statement provides recommendations for COVID-19 vaccination in children and adolescents aged ≥ 5 years with cancer and immunocompromising non-malignant haematological conditions, based on evidence, national and international guidelines and expert opinion.The Australian and New Zealand Children's Haematology/Oncology Group.

Background Respiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development. Methods In this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400). Findings In addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection in-hospital deaths (6800–28 100), and 45 700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs). Interpretation RSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented. Funding EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Respiratory syncytial virus (RSV) is a leading cause of childhood morbidity, however there is no systematic testing in children hospitalised with respiratory symptoms. Therefore, current RSV incidence likely underestimates the true burden. We used probabilistically linked perinatal, hospital, and laboratory records of 321,825 children born in Western Australia (WA), 2000–2012. We generated a predictive model for RSV positivity in hospitalised children aged . From 321,825 hospitalisations, 37,784 were tested for RSV (22.8% positive). Predictors of RSV positivity included younger admission age, male sex, non-Aboriginal ethnicity, a diagnosis of bronchiolitis and longer hospital stay. Our model showed good predictive accuracy (AUROC: 0.87). The respective sensitivity, specificity, positive predictive value and negative predictive values were 58.4%, 92.2%, 68.6% and 88.3%. The predicted incidence rates of hospitalised RSV for children aged

Introduction Influenza is a common cause of acute respiratory infection, and is a major cause of morbidity and mortality. Coronavirus disease 2019 (COVID-19) is an acute respiratory infection that emerged as a pandemic worldwide before the start of the 2020 Australian influenza season. This report summarises the epidemiology of hospitalisations with laboratory-confirmed influenza and COVID-19 during the 2020 influenza season in a sentinel surveillance system. Methods The Influenza Complications Alert Network (FluCAN) is a sentinel hospital-based surveillance program that operates at sites in all jurisdictions in Australia. Influenza and COVID-19 cases were defined as patients hospitalised at sentinel hospitals and confirmed by nucleic acid detection. Results There were 448 patients with COVID-19 admitted between 16 March and 31 December 2020, and only 20 patients with influenza admitted between 1 April and 30 November 2020, to one of 22 FluCAN hospitals. Of the COVID-19 cases, 173 (39%) were > 65 years of age, 36 (8%) were children (< 16 years), 6 (1%) were Aboriginal and Torres Strait Islander peoples, 4 (1%) were pregnant and 289 (65%) had chronic comorbidities. COVID-19 hospital admissions peaked between weeks 13 and 15 (first wave) nationally, and again between weeks 31 and 35 (Victoria), with most admissions represented by those above 40 years of age. Discussion There was an unusually low number of hospital admissions with laboratory-confirmed influenza in this season, compared to recent seasons. This is likely to be due to effective public health interventions and international border closures as a result of a rise in COVID-19 respiratory infections and associated hospitalisations.

Antenatal inactivated influenza (IIV) and pertussis-containing vaccines (dTpa) offer protection against severe respiratory infections for pregnant women and infants6 months of age. Both vaccines are recommended in pregnancy; however, little is known about temporal or jurisdictional trends and predictors of uptake.To identify gaps and predictors of IIV and/or dTpa vaccinations in Australian pregnancies from 2012 to 2017.We conducted a probabilistically linked, multi-jurisdictional population-based cohort study, drawing from perinatal data collections and immunisation databases. We used a generalised linear mixed model with a random effect term to account for clustering of multiple pregnancies within mothers, to calculate vaccination uptake, and identify predictors of uptake by maternal demographic, pregnancy, and health characteristics.Of 591 868 unique pregnancies, IIV uptake was 15%, dTpa 27% and 12% received both vaccines. Pertussis vaccinations in First Nations pregnancies were 20% lower than non-Indigenous pregnancies; dTpa was strongly associated with IIV uptake (risk ratio (RR): 8.60, 95% CI 8.48-8.73). This trend was temporally and jurisdictionally consistent. First Nations women were more likely to have had IIV in pregnancy before the introduction of dTpa in the pregnancy program: (RR: 1.48, 95% CI 1.40-1.57), but less likely after dTpa implementation (RR: 0.78, 95% CI 0.76-0.80).Inequity in vaccine uptake between First Nations and non-Indigenous pregnancies, and dismal rates of vaccination in pregnancy overall need urgent review, particularly before the next influenza pandemic or pertussis outbreak. If antenatal dTpa is driving IIV uptake, changes in antenatal healthcare practices are needed to ensure vaccines are offered equitably and optimally to protect against infection.

BACKGROUND Long-term hepatitis B immunity has been demonstrated following the completion of the primary vaccination series in childhood. Some guidelines recommend a hepatitis B surface antibody (anti-HBs) directed approach following community-acquired needle-stick injury (CANSI) to inform hepatitis B postexposure prophylaxis (PEP) management. We assessed the utility of anti-HBs testing post-CANSI, as well as the costing of, and adherence to PEP at a pediatric hospital. METHODS Children presenting to an Australian tertiary pediatric hospital post-CANSI (2014-2019) were identified retrospectively using medical and laboratory records. Immunization status was obtained from the Australian Immunisation Registry. RESULTS Fifty-six children with CANSI were identified. Of those with immunization records, all had completed hepatitis B vaccinations (n = 52). At presentation, 44% (n = 23) had anti-HBs

Infants aged6 months are vulnerable to severe influenza disease and no vaccine is approved for use in this age group. We aimed to describe the epidemiology, risk factors associated with severe outcomes and management of influenza in Australian infants aged6 months.Incident cases aged6 months of laboratory-confirmed influenza were captured through two national active prospective sentinel hospital-based surveillance systems in Australia from 2011 to 2019, inclusive. Demographic and clinical features, disease risk factors and outcomes (intensive care unit (ICU) admission and length of stay) and oseltamivir use were analysed. The proportion of infant influenza hospitalisations and nosocomial cases among all hospitalisations were also reported.Of 680 hospitalised infants aged6 months, 57.9% were male and 14.5% were Indigenous Australian. Median age was 2.6 months, 19.2% were born premature and 19.0% had a comorbidity, excluding prematurity. Overall, 77.9% had influenza A. Nosocomial cases accounted for 7.8%. ICU admission occurred in 14.7% and oseltamivir was prescribed for 18.8%. Factors associated with ICU admission included age1 month (adjusted odds ratio (aOR) 3.95, 95% confidence interval (CI): 1.47-10.60), comorbidity (aOR 7.69, 95% CI: 4.04-14.64) and prematurity (aOR 2.60, 95% CI: 1.40-4.81). The proportion of infants with influenza among all infant hospitalisations ranged 1.0-2.6% in the 2019 influenza season.Infants aged6 months, and particularly neonates, experience serious disease from influenza. This data underpins the need for preventative strategies such as maternal immunisation and continued investigation into the possibility of safe and efficacious vaccination prior to 6 months of age.

Introduction Influenza vaccination of children with medical comorbidities is critical due their increased risks for severe influenza disease. In Australia, hospitals are an avenue for influenza vaccine delivery to children with comorbidities but are not always effectively utilised. Qualitative enquiry sought to ascertainment the barriers and enablers for influenza vaccination recommendation, delivery, and recording of these children at Australian hospitals. Methods Semi-structured interviews and discussion group sessions were conducted with paediatricians and nurses at four tertiary paediatric specialist hospitals and two general community hospitals in three Australian states. Transcripts from interviews and group sessions were inductively analysed for themes. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was used to explore the elements of each theme and identify potential interventions to increase influenza vaccination recommendation and delivery behaviours by providers. Results Fifteen discussion sessions with 28 paediatricians and 26 nurses, and nine in-depth interviews (five paediatricians and four nurses) were conducted. Two central thematic domains were identified: 1. The interaction between hospital staff and parents/patients for influenza vaccine recommendation, and 2. Vaccination delivery and recording in the hospital environment. Six themes across these domains emerged detailing the importance of dedicated immunisation services, hospital leadership, paediatricians’ vaccine recommendation role, the impact of comorbidities, vaccination recording, and cocooning vaccinations. Supportive hospital leadership, engaged providers, and dedicated immunisation services were identified as essential for influenza vaccination of children with comorbidities in Australian hospital. Conclusion Recommendation of influenza vaccination for Australian children with comorbidities is impacted by the beliefs of paediatricians and the perceived impact of influenza disease on children’s comorbidities. Dedicated immunisation services and supportive hospital leadership were drivers for influenza vaccine delivery at hospitals. Future interventions targeting hospital-based influenza vaccine delivery for children with comorbidities should take a rounded approach targeting providers’ attitudes, the hospital environment and leadership support.

Population-level studies of severe pertussis extending beyond infancy are sparse, and none in the context of antenatal vaccination. We compared hospitalized pertussis cases from birth to 15 years of age before and after introduction of antenatal immunization.Active surveillance of laboratory-confirmed pertussis hospitalizations in a national network of pediatric hospitals in Australia January 2012 to June 2019. Impact of maternal vaccination was assessed by vaccine effectiveness (VE) in cases and test-negative controls with2 months of age and by before-after comparison of age distribution of cases. Among cases eligible for one or more vaccine doses, we examined proportions age-appropriately immunized and with comorbidities by age group.Among 419 eligible cases, the proportion2 months of age significantly decreased from 33.1% in 2012 to 2014 compared with 19.6% in 2016 to 2019 when mothers of only 4 of 17 (23.5%) cases2 months of age had received antenatal vaccination. VE was estimated to be 84.3% (95% CI, 26.1-96.7). Across all years (2012-2019), of 55 cases 4-11 months of age, 21 (38%) had ≥2 vaccine doses, whereas among 155 cases ≥12 months of age, 122 (85.2%) had ≥3 vaccine doses. Prevalence of comorbidities (primarily cardiorespiratory) increased from 5 (2.1%)6 months of age to 36 (24.2%) ≥12 months of age (P0.001), with 6/16 (38%) cases ≥12 months of age who required intensive care having comorbidities.Below the age of 12 months, prevention of severe pertussis will be maximized by high maternal antenatal vaccine uptake and timeliness of infant vaccine doses. Despite full immunization, we found children ≥12 months of age accounted for 27% of hospitalizations15 years, with 24% having comorbities, suggesting new vaccine strategies, such as additional doses or more immunogenic vaccines, require evaluation.