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Melioidosis is an infectious disease caused by the bacterium Burkholderia pseudomallei. Although this environmental organism is endemic in certain regions of Australia, it is not considered endemic in Southern Queensland, where the last case was reported 21 years ago. We report a climate change–associated outbreak of melioidosis occurring during two La Niña events in a region previously considered nonendemic for B. pseudomallei. During a 15-month period, 14 cases of locally acquired melioidosis were identified. Twelve patients were adults (> 50 years), with diabetes mellitus the most common risk factor in 6 of 12 patients (50%). Eleven patients (79%) had direct exposure to floodwaters or the flooded environment. This study suggests an association between climate change and an increased incidence of melioidosis. In addition, this is the first report of environmental sampling and whole-genome analysis to prove endemicity and local acquisition in this region.

Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13-year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection.All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0-16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer-term outcomes via parent survey at least 1 year after initial infection.Forty-three children were identified over the 13-year period, 17 (39.5%) neonates and 26 (60.4%) non-neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2-0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5-3.9). HSV 1 was the predominant serotype in both neonates and non-neonates (9/17, 52.9% neonates and 19/26, 73.1% non-neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty-five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non-neonates) and 20/27 (74.1%) reported long-term neurological morbidity at follow-up (5/9 neonates (55.6%) vs. 15/18 non-neonates (83.3%)). Seven children (two neonates and four non-neonates) with long-term neurological sequelae had no neurological morbidity identified at discharge.Significant long-term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow-up of all children is recommended.

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.

AimThe Australian 'There is no place like home' project is implementing a paediatric low-risk febrile neutropenia (FN) programme across eight paediatric hospitals. We sought to identify the impact of the coronavirus disease 2019 (COVID-19) pandemic on programme implementation.MethodsPaediatric oncology, infectious diseases and emergency medicine health-care workers and parent/carers were surveyed to explore the impact of the COVID-19 pandemic on home-based FN care. Online surveys were distributed nationally to health-care workers involved in care of children with FN and to parents or carers of children with cancer.ResultsSurveys were completed by 78 health-care workers and 32 parents/carers. Overall, 95% of health-care workers had confidence in the safety of home-based FN care, with 35% reporting changes at their own hospitals in response to the pandemic that made them more comfortable with this model. Compared to pre-pandemic, >50% of parent/carers were now more worried about attending the hospital with their child and >80% were interested in receiving home-based FN care. Among both groups, increased telehealth access and acceptance of home-based care, improved patient quality of life and reduced risk of nosocomial infection were identified as programme enablers, while re-direction of resources due to COVID-19 and challenges in implementing change during a crisis were potential barriers.ConclusionThere is strong clinician and parent/carer support for home-based management of low-risk FN across Australia. Changes made to the delivery of cancer care in response to the pandemic have generally increased acceptance for home-based treatments and opportunities exist to leverage these to refine the low-risk FN programme.

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.

Pneumocystis jirovecii is recognized as an opportunistic pathogen in immunosuppressed patients. We report a case of severe Pneumocystis pneumonia (PCP) in an infant with acquired combined immunodeficiency secondary to maternal chemotherapy exposure during the second and third trimesters of pregnancy. The infant required cardiorespiratory support with veno-venous extracorporeal membrane oxygenation (VV-ECMO) for severe respiratory failure. This case highlights the potential for severe acquired immunodeficiency in this patient cohort and further postnatal surveillance is highly recommended.

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.

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.

Objective The current study investigated the social and interpersonal correlates of callous-unemotional (CU) traits using peer nominations. Method Participants (N = 289) were children in Grades 3, 6, and 8 (Mage = 11.47 years, 40.1% male, 64.7% self-identified racial/ethnic minority) from two public school systems in the southern United States. Participants were asked to identify peers they believed fit a number of different characteristics hypothesized to be related to CU traits, in addition to individuals they “liked most” and “liked least.” We also obtained self- and teacher ratings of CU traits and parent and teacher ratings of conduct problems (CP). Results Factor analyses extracted three dimensions from peer nominations developed from past research describing social characteristics related to CU traits—being mean and aloof (Mean/Cold), untrustworthy and not nice (Not Nice), and dominant and manipulative (Desire for Dominance). Results indicated that CU traits were significantly associated with fewer “liked most” and greater “liked least” nominations, but not after controlling for CP. In contrast, both CP and CU traits were significantly independently associated with Mean/Cold nominations, and only CU traits were associated with Not Nice nominations when controlling for CP. Conclusions The findings from the current study suggest that CU traits are largely associated with traditional indices of peer rejection because of their level of CP. However, they contribute independently to perceptions of being mean, aloof, and untrustworthy. Thus, interventions focused on strengthening the social skills of children with elevated CU traits should consider ways to change these negative peer perceptions.

Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of non-albicans species and fluconazole resistance in Australia. These guidelines provide updated evidence-based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non-pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first-line therapy for high-risk patients with IC. Mortality benefit has also been demonstrated for non-pharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.

Children with severe needle phobia find vaccination extremely distressing and can remain unvaccinated, which puts them at an increased risk of contracting and transmitting vaccine preventable disease. Referral to a specialist or hospital service may occur when they cannot be safely vaccinated in the community, but engagement of allied health services can be inconsistent. The aim of the study was to assess the impact of a multidisciplinary, consumer-oriented model of care on vaccinations for needle phobic children.Needle phobic children aged between 6 and 16 years attended multidisciplinary consultation, as part of a care package, to assess previous experiences and determine the level of intervention that was required to support vaccination. A multidisciplinary case meeting followed this appointment and an individualised plan formulated for each patient. The main outcome of the project was rate of successful vaccination.The care package resulted in a successful vaccination rate of 83% (n = 20) with 69 vaccines administered across three clinics. Of those successful, 90% required multiple injections per visit. The majority of patients indicated moderate to high level of anxiety. Supportive care was escalated and de-escalated as tolerated.Results demonstrate the diversity of patients presenting with needle phobia and indicate an individualised, collaborative approach is preferable to a 'one size fits all' model of care. The study highlights a need for the development of guidelines that streamline the assessment and individualisation of procedural anxiety plans to meet patient needs and embed these processes into standard care.

ObjectiveTo present Australia-wide data on paediatric COVID-19 and multisystem inflammatory syndromes to inform health service provision and vaccination prioritisation.DesignProspective, multicentre cohort study.SettingEight tertiary paediatric hospitals across six Australian states and territories in an established research surveillance network—Paediatric Active Enhanced Disease (PAEDS).ParticipantsAll children aged InterventionLaboratory-confirmed SARS-CoV-2 infection.Main outcomeIncidence of severe disease among children with COVID-19, PIMS-TS and KD-TS. We also compared KD epidemiology before and during the COVID-19 pandemic.ResultsAmong 386 children with SARS-CoV-2 infection, 381 (98.7%) had COVID-19 (median 6.3 years (IQR 2.1–12.8),53.3% male) and 5 (1.3%) had multisystem inflammatory syndromes (PIMS-TS, n=4; KD-TS, n=1) (median 7.9 years (IQR 7.8–9.8)). Most children with COVID-19 (n=278; 73%) were Australian-born from jurisdictions with highest community transmission. Comorbidities were present in 72 (18.9%); cardiac and respiratory comorbidities were most common (n=32/72;44%). 37 (9.7%) children with COVID-19 were hospitalised, and two (0.5%) required intensive care. Postinfective inflammatory syndromes (PIMS-TS/KD-TS) were uncommon (n=5; 1.3%), all were hospitalised and three (3/5; 60%) required intensive care management. All children recovered and there were no deaths. KD incidence remained stable during the pandemic compared with prepandemic.ConclusionsMost children with COVID-19 had mild disease. Severe disease was less frequent than reported in high prevalence settings. Preventative strategies, such as vaccination, including children and adolescents, could reduce both the acute and postinfective manifestations of the disease.

ObjectivesTimely intravenous-to-oral antibiotic switching for children is important for paediatric antimicrobial stewardship (AMS). However, low decision-making confidence and fragmentation of patient care can hamper implementation, with difficulties heightened regionally where AMS programmes for children are lacking. The aim of this study was to develop and evaluate user-led creation and implementation of an intervention package for early intravenous-to-oral switching at regional hospitals in Queensland, Australia.DesignGuided by theory, a four-phase approach was used to: (1) develop multifaceted intervention materials; (2) review materials and their usage through stakeholders; (3) adapt materials based on user-feedback and (4) qualitatively evaluate health workers experiences at 6 months postintervention.SettingSeven regional hospitals in Queensland, Australia.ParticipantsPhase 2 included 15 stakeholders; health workers and patient representatives (patient-guardians and Indigenous liaison officers). Phase 4 included 20 health workers across the seven intervention sites.ResultsContent analysis of health worker and parent/guardian reviews identified the ‘perceived utility of materials’ and ‘possible barriers to use’. ‘Recommendations and strategies for improvement’ provided adjustments for the materials that were able to be tailored to individual practice. Postintervention interviews generated three overarching themes that combined facilitators and barriers to switching: (1) application of materials, (2) education and support, and (3) team dynamics. Overall, despite difficulties with turnover and problems with the medical hierarchy, interventions aided and empowered antibiotic therapy decision-making and enhanced education and self-reflection.ConclusionsDespite structural barriers to AMS for switching from intravenous-to-oral antibiotics in paediatric patients, offering a tailored multifaceted intervention was reported to provide support and confidence to adjust practice across a diverse set of health workers in regional areas. Future AMS activities should be guided by users and provide opportunities for tailoring tools to practice setting and patients’ requirements.

Background: Children with comorbidities are at greater risk of severe influenza outcomes compared with healthy children. In Australia, influenza vaccination was funded for those with comorbidities from 2010 and all children aged

Background The impact febrile neutropenia (FN) has on the health-related quality of life (HRQoL) of children with cancer and their families is poorly understood. We sought to characterize the course of child and parent HRQoL during and following FN episodes. Method Data on HRQoL were collected in the multisite Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) study. Participants were enrolled between November 2016 to January 2018. The Child Health Utility (CHU9D) was used to assess HRQoL in children (N = 167 FN events) and the Assessment of Quality of Life (AQoL-8D) was used to assess HRQoL parents (N = 218 FN events) at three time points: 0–3 days, 7-days and 30-days following the onset of FN. Group-based trajectory modeling (GBTM) was used to characterize the course of HRQoL. Findings For children, three distinct groups were identified: persistently low HRQoL over the 30-day course of follow-up (chronic: N = 78/167; 47%), increasing HRQoL after the onset of FN to 30 days follow-up (recovering: N = 36/167; 22%), and persistently high HRQoL at all three timepoints (resilient: N = 53/167; 32%). Applying these definitions, parents were classified into two distinct groups: chronic (N = 107/218, 49%) and resilient (N = 111/218, 51%). The child being male, having solid cancer, the presence of financial stress, and relationship difficulties between the parent and child were significant predictors of chronic group membership for both parents and children. Children classified as high-risk FN were significantly more likely to belong to the recovery group. Being female, having blood cancers and the absence of financial or relationship difficulties were predictive of both parents and children being in the resilient group. Interpretation Approximately half the children and parents had chronically low HRQoL scores, which did not improve following resolution of the FN episode. The child's sex, cancer type, and presence of financial and relationship stress were predictive of chronic group membership for both parents and children. These families may benefit from increased financial and psychosocial support during anti-cancer treatment. Funding National Health and Medical Research Council Grant (APP1104527).

Candida auris is an emerging drug-resistant yeast responsible for hospital outbreaks. This statement reviews the evidence regarding diagnosis, treatment and prevention of this organism and provides consensus recommendations for clinicians and microbiologists in Australia and New Zealand. C. auris has been isolated in over 30 countries (including Australia). Bloodstream infections are the most frequently reported infections. Infections have crude mortality of 30-60%. Acquisition is generally healthcare-associated and risks include underlying chronic disease, immunocompromise and presence of indwelling medical devices. C. auris may be misidentified by conventional phenotypic methods. Matrix-assisted laser desorption ionisation time-of-flight mass spectrometry or sequencing of the internal transcribed spacer regions and/or the D1/D2 regions of the 28S ribosomal DNA are therefore required for definitive laboratory identification. Antifungal drug resistance, particularly to fluconazole, is common, with variable resistance to amphotericin B and echinocandins. Echinocandins are currently recommended as first-line therapy for infection in adults and children ≥2 months of age. For neonates and infants

Encephalitis is most often caused by a variety of infectious agents, the identity of which is commonly determined through diagnostic tests utilising cerebrospinal fluid (CSF). Immune-mediated disorders are also a differential in encephalitis cases. We investigated the clinical characteristics and potential aetiological agents of unexplained encephalitis through metagenomic next-generation sequencing of residual clinical samples of multiple tissue types and independent clinical review. A total of 43 specimens, from both sterile and non-sterile sites, were collected from 18 encephalitis cases with no cause identified by the Australian Childhood Encephalitis study. Samples were subjected to total RNA sequencing to determine the presence and abundance of potential pathogens, to reveal mixed infections, pathogen genotypes, and epidemiological origins, and to describe the possible aetiologies of unexplained encephalitis. From this, we identified five RNA and two DNA viruses associated with human infection from both non-sterile (nasopharyngeal aspirates, nose/throat swabs, urine, stool rectal swab) and sterile (cerebrospinal fluid, blood) sites. These comprised two human rhinoviruses, two human seasonal coronaviruses, two polyomaviruses and one picobirnavirus. With the exception of picobirnavirus all have been previously associated with respiratory disease. Human rhinovirus and seasonal coronaviruses may be responsible for five of the encephalitis cases reported here. Immune-mediated encephalitis was considered clinically likely in six cases and RNA sequencing did not identify a possible pathogen in these cases. The aetiology remained unknown in nine cases. Our study emphasises the importance of respiratory viruses in the aetiology of unexplained child encephalitis and suggests that the routine inclusion of non-CNS sampling in encephalitis clinical guidelines/protocols could improve the diagnostic yield.Author SummaryEncephalitis is caused by both infectious agents and auto-immune disorders. However, the aetiological agents, including viruses, remain unknown in around half the cases of encephalitis in many cohorts. Importantly, diagnostic tests are usually based on the analysis of cerebrospinal fluid which may limit their utility. We used a combination of meta-transcriptomic sequencing and independent clinical review to identify the potential causative pathogens in cases of unexplained childhood encephalitis. Accordingly, we identified seven viruses associated with both sterile and non-sterile sampling sites. Human rhinovirus and seasonal coronaviruses were considered as most likely responsible for five of the 18 encephalitis cases studied, while immune-mediated encephalitis was considered the cause in six cases, and we were unable to determine the aetiology in nine cases. Overall, we demonstrate the role of respiratory viruses as a cause of unexplained encephalitis and that sampling sites other than cerebrospinal fluid is of diagnostic value.

Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children.IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated.A total of 181 patients were identified, with most (115, 63.5%)5 years old. The mean annual minimum incidence rate was 1.6 (95% confidence interval: 1.1-2.3) per 100,000 children across the study period. An epidemiological correlation with the seasonal burden of influenza was noted. Contact prophylaxis was not consistently offered. Of 96 patients with emm-typing results available, 72.9% showed emm-1, -4 or - 12.Robust surveillance systems and cohesive patient management guidelines are needed. Making iGAS disease nationally notifiable would help facilitate this. Influenza vaccination may contribute to reducing seasonal increases in iGAS incidence. The burden of disease emphasises the need for ongoing progress in GAS vaccine development.

Introduction. Mycobacterium abscessus complex (MABSC) is an environmental organism and opportunistic pathogen. MABSC pulmonary infections in people with cystic fibrosis are of growing clinical concern. Resistance data guide the use of macrolides and amikacin in MABSC pulmonary disease treatment. MABSC can acquire resistance against macrolides or amikacin via 23S or 16S rRNA gene mutations, respectively. Gap Statement. Current culture-based methods for MABSC detection and antibiotic resistance characterization are typically prolonged, limiting their utility to directly inform treatment or clinical trials. Culture-independent molecular methods may help address this limitation. Aim. To develop real-time PCR assays for characterization of key 23S or 16S rRNA gene mutations associated with constitutive resistance in MABSC. Methodology. We designed two real-time PCR assays to detect the key 23S and 16S rRNA gene mutations. The highly conserved nature of rRNA genes was a major design challenge. To reduce potential cross-reactivity, primers included non-template bases and targeted single-nucleotide polymorphisms unique to MABSC. We applied these assays, as well as a previously developed real-time PCR assay for MABSC detection, to 968 respiratory samples from people with cystic fibrosis. The results from the molecular methods were compared to those for gold standard culture methods and 23S and 16S rRNA gene sequencing. Results.The real-time PCR MABSC detection assay provided a sensitivity of 83.8 % and a specificity of 97.8 % compared to culture. The results from the real-time PCR resistance detection assays were mostly concordant (>77.4 %) with cultured isolate sequencing. The real-time PCR resistance detection assays identified several samples harbouring both resistant and susceptible MABSC, while culture-dependent methods only identified susceptible MABSC in these samples. Conclusion. Using the molecular methods described here, results for health care providers or researchers could be available days or weeks earlier than is currently possible via culture-based antibiotic susceptibility testing.

Background: The condition known as 22q11 microdeletion syndrome has a broad phenotypic spectrum, with many affected individuals experiencing mild-to-moderate immunodeficiency. Currently, there are significant variations in live vaccine practices and immunological testing prior to live vaccine administration due to safety concerns and limited established guidelines. Methods: Queensland Children’s Hospital (QCH) Child Development Unit, offers a state-wide 22q11 microdeletion clinic. This is a retrospective single-centre review, capturing the majority of children with 22q11 microdeletion in Queensland, Australia. We describe the live vaccination status of 134 children, age 0 to 18 years under our care between 2000 and 2018, adverse events following immunisation (AEFI) and the proportion of children who received additional pneumococcal coverage. An immunological investigation pathway prior to live vaccine administration is proposed. Results: Of the 134 children, 124 were eligible for live vaccinations as per the Australian National Immunisation Program: 82% had received dose one of measles, mumps and rubella (MMR) vaccine, 77% had completed MMR dose two and 66% had completed varicella immunisation. There were no AEFI notifications reported. Of the total sample of children, 18% received a fourth dose of conjugate pneumococcal vaccine (Prevenar 7 or 13) and 16% received a dose of Pneumovax 23 from 4 years of age. Immunology workup practices were demonstrated to vary widely prior to live vaccine administration. Most patients’ immune profiles were consistent with mild-to-moderate immunodeficiency. Conclusion: We propose an immunological investigation and vaccination pathway with the aim of providing guidance and consistency to clinicians caring for children with 22q11 microdeletion.

Background There are few longitudinal studies of seasonal influenza-associated neurological disease (IAND) and none from the Southern Hemisphere. Methods We extracted prospectively acquired Australian surveillance data from 2 studies nested within the Paediatric Active Enhanced Disease Surveillance (PAEDS) network: the Influenza Complications Alert Network (FluCAN) study and the Australian Childhood Encephalitis (ACE) study between 2013 and 2015. We described the clinical features and severity of IAND in children, including influenza-associated encephalitis/encephalopathy (IAE). We calculated the proportion of hospitalized influenza that is associated with IAND and IAE, and incidence of IAE. Results Over 3 influenza seasons, we identified 54 cases of IAND at 2 tertiary children's hospitals from Australia that accounted for 7.6% of hospitalized influenza. These included 10 cases of IAE (1.4% hospitalized influenza). The mean annual incidence of IAE among Australian children (aged ≤14 years) was 2.8 per 1000000. The spectrum of IAND was broad and included IAE (n = 10) including distinct acute encephalopathy syndromes, simple febrile seizures (n = 14), other seizures (n = 16), acute ataxia (n = 4), and other subacute syndromes (transverse myelitis [n = 1], opsoclonus myoclonus [n = 1]). Two-thirds of children with IAND were aged ≤4 years; less than half had preexisting neurological disease or other risk factors for severe influenza. IAE caused death or neurological morbidity in half of cases. Conclusions Seasonal influenza is an important cause of acute neurological disease in Australian children. The spectrum of seasonal IAND appears similar to that described during the 2009 H1N1 pandemic. IAE is associated with high morbidity and mortality.

BACKGROUND: Understanding paediatric tuberculosis (TB) is important, as children with TB typically reflect recent community transmission. Children pose unique diagnostic challenges and are at risk of developing severe disseminated infection. OBJECTIVE : To describe the epidemiology, presentation and outcomes of children with TB disease in Queensland. DESIGN: This is a retrospective case series of children diagnosed with TB aged 0-16 years notified in 2005-2014. Data collected in the Queensland Notifiable Conditions System were extracted and analysed. RESULT S : Of 127 children diagnosed with TB, 16 were Australian-born (including 12 Indigenous Queenslanders), 41 were overseas-born permanent and temporary residents and 70 were cross-border Papua New Guinea (PNG) children; 88 children had pulmonary disease (with/without other sites) and 39 had extrapulmonary disease only, with lymph node TB the predominant extra-pulmonary site; 70.1% of children had laboratory confirmation; and 14 cross-border children had multidrug-resistant TB. Treatment outcomes among children residing in Australia were good (100% among Australian-born and 97.2% among permanent and temporary residents), but they were less favourable among PNG children diagnosed in the Torres Strait Protected Zone (76.6%). CONCLUS ION: Queensland has unique challenges in TB control, with a high proportion of cross-border diagnoses and over-representation of Indigenous children. Vigilance is needed given the wide spectrum of clinical presentation, particularly in high-risk communities.

This study describes a successful, targeted intervention in central venous access device routine care to decrease central line-associated bloodstream infection. Taurolidine-citrate locks significantly reduced the rate of central line-associated bloodstream infection, particularly Gram-negative organisms without adverse events.

Objectives: Invasive group A Streptococcus (iGAS) disease is serious and sometimes life-threatening. The Paediatric Active Enhanced Disease Surveillance (PAEDS) Network collects voluntary notifications from seven major Australian paediatric hospitals on patients with certain conditions, including iGAS disease. Our aims were to: 1) Describe the epidemiological distribution of paediatric iGAS disease in Australia and correlate this with influenza notifications, 2) Identify GAS strains commonly associated with invasive disease in children. Methods: IGAS and influenza notification data were obtained (from the PAEDS Network and the Australian Institute of Health and Welfare, respectively, for the period 1 July 2016 to 30 June 2018). Included iGAS patients had GAS isolated from a normally sterile body site. Data were described according to selected clinical and demographic characteristics, including by age group and Australian State, with proportions and minimum incidence rates estimated. Results: A total of 181 patients were identified, with most (115, 63.5%), SCOPUS: ar.j, info:eu-repo/semantics/published

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

Background Invasive fungal infections (IFI) are an important complication of acute lymphoblastic leukaemia (ALL) treatment. Our study describes the prevalence and outcomes of IFI in children with ALL. Methods IFI episodes in children with primary or relapsed ALL, identified for The Epidemiology and Risk Factors for Invasive Fungal Infections in Immunocompromised Children study, were analysed. IFI were classified according to European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group criteria with a 'modified-possible' category included. Results A total of 123 IFI episodes in 119 patients with ALL were included. A proven, probable, possible and modified-possible IFI was diagnosed in 56 (45.5%), 22 (17.9%), 39 (31.7%) and six (4.9%) episodes, respectively. The prevalence was 9.7% (95% confidence interval [CI] 8-11.4%) overall and 23.5% (95% CI 14.5-32.5%) for relapsed/refractory ALL. For non-relapsed ALL, the IFI prevalence was significantly higher for children with high-risk compared to standard-risk ALL (14.5% vs 7.3%, P = .009), and IFI were more common during induction, consolidation and delayed intensification phases. Mould infections occurred more frequently than non-mould infections. Thirteen children (10.9%) died within 6 months of IFI diagnosis with five deaths (4.2%) attributable to an IFI. Conclusions IFI is more common in children with high-risk ALL and in relapsed disease. Overall survival was encouraging, with IFI contributing to very few deaths.

Background We aimed to determine the contemporary causes, clinical features, and short-term outcome of encephalitis in Australian children. Methods We prospectively identified children (≤14 years of age) admitted with suspected encephalitis at 5 major pediatric hospitals nationally between May 2013 and December 2016 using the Paediatric Active Enhanced Disease Surveillance (PAEDS) Network. A multidisciplinary expert panel reviewed cases and categorized them using published definitions. Confirmed encephalitis cases were categorized into etiologic subgroups. Results From 526 cases of suspected encephalitis, 287 children met criteria for confirmed encephalitis: 57% (95% confidence interval [CI], 52%–63%) had infectious causes, 10% enterovirus, 10% parechovirus, 8% bacterial meningoencephalitis, 6% influenza, 6% herpes simplex virus (HSV), and 6% Mycoplasma pneumoniae; 25% (95% CI, 20%–30%) had immune-mediated encephalitis, 18% acute disseminated encephalomyelitis, and 6% anti-N-methyl-d-aspartate receptor encephalitis; and 17% (95% CI, 13%–21%) had an unknown cause. Infectious encephalitis occurred in younger children (median age, 1.7 years [interquartile range {IQR}, 0.1–6.9]) compared with immune-mediated encephalitis (median age, 7.6 years [IQR, 4.6–12.4]). Varicella zoster virus encephalitis was infrequent following high vaccination coverage since 2007. Thirteen children (5%) died: 11 with infectious causes (2 influenza; 2 human herpesvirus 6; 2 group B Streptococcus; 2 Streptococcus pneumoniae; 1 HSV; 1 parechovirus; 1 enterovirus) and 2 with no cause identified. Twenty-seven percent (95% CI, 21%–31%) of children showed moderate to severe neurological sequelae at discharge. Conclusions Epidemic viral infections predominated as causes of childhood encephalitis in Australia. The leading causes include vaccine-preventable diseases. There were significant differences in age, clinical features, and outcome among leading causes. Mortality or short-term neurological morbidity occurred in one-third of cases.

The aim of the present study was to review the potential impacts and barriers to upscaling a pilot congenital Cytomegalovirus (cCMV) screening program into a state-wide permanent universal newborn hearing screening (UNHS) program.This study reviewed the outcomes of the cCMV screening program pilot operating at three maternity hospitals to standard state-wide laboratory notifications in Queensland, Australia between August 2014 to April 2018. Stakeholder interviews were also conducted to inform state-wide program implementation.Of the 485 infants tested for CMV on a saliva swab at the pilot sites, 4 (0.8%) returned a positive result. Review of the state-wide laboratory infant CMV PCR notifications for the same time-period revealed more than half of infants with cCMV (63.7%) would not have been detected under a state-wide targeted screening program as they either passed newborn hearing screening, were deceased, symptomatic, or were born34 weeks gestational age. Barriers to state-wide program implementation included program-level factors (timing of the cCMV screen, funding, cross-agency communication, workforce and training) and community-level factors (low public cCMV awareness and prevalence).Although cCMV screening alongside UNHS is achievable, a number of barriers need to be addressed prior to state-wide program implementation.

Mucormycosis is the second most common cause of invasive mould infection and causes disease in diverse hosts, including those who are immuno-competent. We conducted a multicentre retrospective study of proven and probable cases of mucormycosis diagnosed between 2004-2012 to determine the epidemiology and outcome determinants in Australia. Seventy-four cases were identified (63 proven, 11 probable). The majority (54.1%) were caused by Rhizopus spp. Patients who sustained trauma were more likely to have non-Rhizopus infections relative to patients without trauma (OR 9.0, p 0.001, 95% CI 2.1-42.8). Haematological malignancy (48.6%), chemotherapy (42.9%), corticosteroids (52.7%), diabetes mellitus (27%) and trauma (22.9%) were the most common co-morbidities or risk factors. Rheumatological/autoimmune disorders occurred in nine (12.1%) instances. Eight (10.8%) cases had no underlying co-morbidity and were more likely to have associated trauma (7/8; 87.5% versus 10/66; 15.2%; p

Febrile neutropenia requires prompt assessment and antibiotic administration and is the most common reason for unexpected hospital admission in pediatric oncology. Parents are expected to be vigilant and “drop everything” to take their child to their nearest hospital for assessment if fever occurs. Delays in antibiotic administration are associated with poorer outcomes; however, delays are common. Our aim was to understand and describe the lived experience of parents of children with cancer who received treatment for fever with confirmed/suspected neutropenia. We used descriptive phenomenological concepts to undertake and analyze interviews with parents, who were asked to describe their recent experience of hospitalization in Queensland, Australia. Nine participants were interviewed. Five children were treated in the tertiary treating center and four were treated in smaller regional towns. Three main categories were identified that shaped and characterized parents’ experiences: being heard, confidence in capabilities of health care professionals, and living with anticipated distress and uncertainty. Parents’ experiences were related to the level they needed to advocate for their child’s care across all themes. Familiarity with health care professionals increased confidence and improved parents’ experiences. Maintaining vigilance and managing the child and family’s response to an unexpected admission had a substantial negative effect on parents. Understanding parents’ experiences and perceptions of the management of febrile neutropenia adds to the current body of knowledge and offers potential new insights to improve clinical practice.

Background In 2017, Australia experienced record influenza notifications. Two surveillance programs combined to summarize the epidemiology of hospitalized influenza in children and report on vaccine effectiveness (VE) in the context of a limited nationally funded vaccination program. Methods Subjects were prospectively recruited (April-October 2017). Case patients were children aged ≤16 years admitted to 11 hospitals with an acute respiratory illness and laboratory-confirmed influenza. Controls were hospitalized with acute respiratory illness and tested negative for influenza. VE estimates were calculated using the test-negative design. Results A total of 1268 children were hospitalized with influenza: 31.5% were

To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use.Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study.Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012.Children and adolescents who were inpatients at 8 am on the day of the survey.Quantity and quality of antimicrobial prescribing.Of 1373 patients, 631 (46%) were prescribed at least one antimicrobial agent, 198 (31%) of whom were 1 year old. The highest antimicrobial prescribing rates were in haematology and oncology wards (76% [95/125]) and paediatric intensive care units (55% [44/80]). Of 1174 antimicrobial prescriptions, 550 (47%) were for community-acquired infections, 175 (15%) were for hospital-acquired infections and 437 (37%) were for prophylaxis. Empirical treatment accounted for 72% of antimicrobial prescriptions for community-acquired infections and 58% for hospital-acquired infections (395 and 102 prescriptions, respectively). A total of 915 prescriptions (78%) were for antibacterials; antifungals and antivirals were predominantly used for prophylaxis. The most commonly prescribed antibacterials were narrow-spectrum penicillins (18% [164 prescriptions]), β-lactam-β-lactamase inhibitor combinations (15% [136]) and aminoglycosides (14% [128]). Overall, 957 prescriptions (82%) were deemed appropriate, but this varied between hospitals (range, 66% [74/112]) to 95% [165/174]) and specialties (range, 65% [122/187] to 94% [204/217]). Among surgical patients, 65 of 187 antimicrobial prescriptions (35%) were deemed inappropriate, and a common reason for this was excessive prophylaxis duration.A point prevalence survey is a useful cross-sectional method for quantifying antimicrobial use in paediatric populations. The value is significantly augmented by adding assessment of prescribing quality.

Background: The comparative yield of respiratory virus detection from nasopharyngeal aspirate (NPA) versus bronchoalveolar lavage (BAL) is uncertain. Furthermore, the significance of virus detection and its relationship to lower airway neutrophilic inflammation is poorly studied. Objectives: To evaluate the sensitivity, specificity and predictive values of NPA for detecting respiratory viruses in BAL; and to determine the relationship between viruses and lower airway neutrophilia in children with non-acute respiratory illness. Study design: 150 paired NPA and BAL samples were obtained from 75 children aged

Rationale and aim To compare clinical features and management of paediatric community-acquired pneumonia (PCAP) following the publication of UK pneumonia guidelines in 2002 with data from a similar survey at the same hospitals in 2001–2002 (pre-guidelines). Methods A prospective survey of 11 hospitals in Northern England was undertaken during 2008–2009. Clinical and laboratory data were recorded on children aged ≤16 years who presented with clinical and radiological features of pneumonia. Results 542 children were included. There was a reduction in all investigations performed (P

To observe and report rates of, and reasons for, parents' refusal to consent to the participation of their children in appropriate clinical research. The parents of children admitted to hospital with a diagnosis of pneumonia or of empyema were asked for informed consent to research involving blood, urine and nasopharyngeal secretion samples from their child. Circumstances and numbers of agreements and refusals were compared and underlying reasons suggested. Of 144 consent requests, ten were refused, which appeared to be linked to: not wanting the child to undergo further tests, lack of interest in participating in studies, research possibly delaying discharge, and anxiety regarding written consent and the length of information sheets. Severity of the child's illness appeared to determine the parent's decision. Involvement and assistance of non-research nursing and medical staff and previous introductions to the researchers are helpful. The timing and setting for the consent process should be selected carefully. Adequate, accessible study information for parents and children contributes to successful recruitment of participants.

SUMMARYThe aim of this study was to investigate spatial variation in risk of hospitalization in childhood pneumonia and empyema in the North of England and associated risk factors. Data on childhood (0–14 years) hospital admissions with a diagnosis pneumonia or empyema were linked to postcode districts. Bayesian conditional autoregressive models were used to evaluate spatial variation and the relevance of specific spatial covariates in an area-based study using postcode as the areal unit. There was a sixfold variation in the risk of hospitalization due to pneumonia across the study region. Variation in risk was associated with material deprivation, Child Well-being Index (CWI) health domain score, number of children requiring local authority support, and distance to hospital. No significant spatial variation in risk for empyema was found.

Introduction: Prior studies on Protracted Bacterial Bronchitis (PBB) link wet cough with bacterial infection and inflammation of the lower airways, but the role of viral infection is not well defined. We hypothesized that viral-bacterial co-infection is more common in children with wet cough and is associated with heightened airway neutrophilia. Methods: We prospectively recruited 232 children undergoing elective fl exible bronchoscopy. Participants were grouped into wet, dry or no cough groups. Broncho-alveolar lavage (BAL) and clinical data, including presence, nature and duration of cough and key demographic factors, were collected. Results: Children with wet cough were more likely to have lower airway bacterial infection (OR 2.6, p = 0.001), viral infection (OR 2.04, p = 0.045) and viral-bacterial co-infection (OR 2.65, p = 0.042) compared to those with dry or no cough. Viral-bacterial co-infection was associated with the highest median %neutrophils (33.5%) compared to bacteria only, virus/es only and no infection (20%, 18% and 6%, respectively, p < 0.0001). Conclusion: Lower airway infection (viral and/or bacterial) is more common in children with wet cough. The greatest neutrophilic airway infl ammation is seen in children with viral-bacterial co-infection of their lower airways. Support: Financial Markets Foundation for children (project), Allen & Hanburys, QCMRI and NHMRC (for DW), NHMRC (for JU and AC). Conflict of Interest: None.

SUMMARYIn September 2006, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the UK immunization programme. We aimed to evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. A prospective survey was undertaken in 2008–2009 at 11 hospitals in North East England of children aged 0–16 years with radiologically confirmed pneumonia. Data were compared to those from a similar survey undertaken in the same hospitals in 2001–2002. A total of 542 children were enrolled, of which 74% were aged

Classic human polyomaviruses (JC and BK viruses) become pathogenic when reactivating from latency. For the rare skin disease trichodysplasia spinulosa, we show that manifestations of the causative polyomavirus (TSPyV) occur during primary infection of the immunosuppressed host. High TSPyV loads in blood and cerebrospinal fluid, sometimes coinciding with cerebral lesions and neuroendocrine symptoms, marked the acute phase of trichodysplasia spinulosa, whereas initiation and maturation of TSPyV seroresponses occurred in the convalescent phase. TSPyV genomes lacked the rearrangements typical for reactivating polyomaviruses. These findings demonstrate the clinical importance of primary infection with this rapidly expanding group of human viruses and explain the rarity of some novel polyomavirus-associated diseases.