Evaluation of Pediatric HIV Postexposure Prophylaxis Guideline Following Child Sexual Assault in Western Australia.

BACKGROUND: HIV postexposure prophylaxis (PEP) following child sexual assault (CSA) is recommended in select cases. High rates of poor adherence to PEP are reported. We evaluated adherence to the recommended management of children following CSA at the tertiary pediatric facility in Western Australia and compared our approach with international guidelines. METHODS: Medical records were reviewed for all children <16 years old assessed at Perth Children's Hospital between October 1, 2016 and November 30, 2020 following alleged CSA. Data, including exposure type, PEP adherence and follow-up, were collected. A review of contemporary national and international PEP guidelines was undertaken in parallel. RESULTS: There were 511 alleged CSA events over the study period; 62/511 (12%) were appropriately risk-assessed as requiring PEP by the treating clinician. PEP was not prescribed in 8/62 (13%) events, with a reason documented for 6/8 (75%). Overall, less than half of children who were eligible for PEP were adherent to the 28-day regimen (23/54, 43%). Gastrointestinal upset contributed to early cessation in 5/54 (9%). Final 3-month blood-borne virus serology results were available in less than one in 3 children. A review of international clinical practice revealed significant heterogeneity of criteria for the provision of PEP and a paucity of pediatric-specific data. CONCLUSIONS: We identified several areas of our PEP management that required strengthening, with limited direction available in current international guidelines. We have adopted a broader use of fixed drug combinations and implemented a multifaceted follow-up program. It will be essential to review the impact of these changes.

The Changing Detection Rate of Respiratory Syncytial Virus in Adults in Western Australia between 2017 and 2023.

The incidence of respiratory syncytial virus (RSV) in adults is inadequately defined and the impact of SARS-CoV-2-related non-pharmaceutical interventions (NPIs) is underexplored. Using laboratory data, we described the detection rate of RSV in adults ≥16 years in Western Australia (WA) between 2017 and 2023. With the exception of 2020, RSV detections rose annually between 2017 and 2023, reaching 50.7 per 100,000 in 2023 (95% confidence interval [CI], 47.9-53.8). RSV testing expanded considerably across the study period, with the testing in 2023 more than five times the 2017 total. The detection rate was highest in adults ≥60 years between 2017 and 2019, particularly those ≥75 years. Following 2020, the detections in all age groups increased, with the highest detection rate in 2023 in those ≥75-years (199.5 per 100,000; 95% CI, 180.5-220). NPIs significantly impacted RSV seasonality; the preceding winter pattern was disrupted, resulting in an absent 2020 winter season and two major summer seasons in 2020/21 and 2021/22. The RSV season began to realign in 2022, reverting to a winter seasonal pattern in 2023 and the largest season in the study period. Ongoing surveillance will be required to understand the stability of these increases and to delineate the impact of new immunisation strategies.

Head-to-Head Comparison Between Respiratory Syncytial Virus and Human Metapneumovirus Bronchiolitis in the Setting of Increased Viral Testing.

We compared the epidemiology, severity and management of hospitalized respiratory syncytial virus (n = 305) and human metapneumovirus (n = 39) bronchiolitis in a setting with high respiratory virus testing (95% of admissions tested). Respiratory syncytial virus-positive infants were younger and tended to require more hydration support and longer hospital stays compared to human metapneumovirus-positive infants. Respiratory support requirements were similar between groups despite significant age differences.

Respiratory Syncytial Virus Reinfections in Children in Western Australia.

Respiratory syncytial virus (RSV) reinfection in children is poorly understood. We examined the incidence, characteristics, and outcomes of hospital-attended RSV reinfections in children <16 years in Western Australia between 2012 and 2022. Individuals with repeat RSV detections ≥56 days apart were identified using laboratory data. The incidence of reinfection in the first five years of life was estimated using the total birth population from 2012 to 2017. Clinical data on a subset of reinfection episodes were obtained from two metropolitan pediatric centers. A total of 466 children with hospital-attended reinfections were identified. The median interval between RSV detections was 460 days (interquartile range: 324, 812), with a reinfection rate of 95 per 100,000 individuals (95% confidence interval: 82, 109). Reinfection was most common in children who experienced their first RSV detection <6 months of age. Predisposing factors were identified in 56% of children; children with predisposing factors were older at first and second detections, were more likely to be admitted, and had a longer length of stay. This study highlights the significant burden of hospital-attended RSV reinfections in children with and without predisposing factors. Expanded surveillance with in-depth clinical data is required to further characterize the impact of RSV reinfection.

A surge in human metapneumovirus paediatric respiratory admissions in Western Australia following the reduction of SARS-CoV-2 non-pharmaceutical interventions.

AIM: Western Australian laboratory data demonstrated a decrease in human metapneumovirus (hMPV) detections through 2020 associated with SARS-CoV-2-related non-pharmaceutical interventions (NPIs), followed by a subsequent surge in metropolitan region in mid-2021. We aimed to assess the impact of the surge in hMPV on paediatric hospital admissions and the contribution of changes in testing. METHODS: All respiratory-coded admissions of children aged <16 years at a tertiary paediatric centre between 2017 and 2021 were matched with respiratory virus testing data. Patients were grouped by age at presentation and by ICD-10 AM codes into bronchiolitis, other acute lower respiratory infection (OALRI), wheeze and upper respiratory tract infection (URTI). For analysis, 2017-2019 was utilised as a baseline period. RESULTS: hMPV-positive admissions in 2021 were more than 2.8 times baseline. The largest increase in incidence was observed in the 1-4 years group (incidence rate ratio (IRR) 3.8; 95% confidence interval (CI): 2.5-5.9) and in OALRI clinical phenotype (IRR 2.8; 95% CI: 1.8-4.2). The proportion of respiratory-coded admissions tested for hMPV in 2021 doubled (32-66.2%, P < 0.001), with the greatest increase in wheeze (12-75% in 2021, P < 0.001). hMPV test percentage positivity in 2021 was higher than in the baseline period (7.6% vs. 10.1% in 2021, P = 0.004). CONCLUSION: The absence and subsequent surge underline the susceptibility of hMPV to NPIs. Increased hMPV-positive admissions in 2021 can be partially attributable to testing, but test-positivity remained high, consistent with a genuine increase. Continued comprehensive testing will help ascertain true burden of hMPV respiratory diseases.

The seasonality of respiratory syncytial virus in Western Australia prior to implementation of SARS-CoV-2 non-pharmaceutical interventions.

Background: Respiratory syncytial virus (RSV) seasonality is dependent on the local climate. We assessed the stability of RSV seasonality prior to the SARS-CoV-2 pandemic in Western Australia (WA), a state spanning temperate and tropical regions. Method: RSV laboratory testing data were collected from January 2012 to December 2019. WA was divided into three regions determined by population density and climate: Metropolitan, Northern and Southern. Season threshold was calculated per region at 1.2% annual cases, with onset the first of ≥2 weeks above this threshold and offset as the last week before ≥2 weeks below. Results: The detection rate of RSV in WA was 6.3/10,000. The Northern region had the highest detection rate (15/10,000), more than 2.5 times the Metropolitan region (detection rate ratio 2.7; 95% CI, 2.6-2.9). Test percentage positive was similar in the Metropolitan (8.6%) and Southern (8.7%) regions, with the lowest in the Northern region (8.1%). RSV seasons in the Metropolitan and Southern regions occurred annually, with a single peak and had consistent timing and intensity. The Northern tropical region did not experience a distinct season. Proportion of RSV A to RSV B in the Northern region differed from the Metropolitan region in 5 of the 8 years studied. Conclusions: Detection rate of RSV in WA is high, especially in the Northern region, where climate, an expanded at-risk population and increased testing may have contributed to greater numbers. Before the SARS-CoV-2 pandemic, RSV seasonality in WA was consistent in timing and intensity for the Metropolitan and Southern regions.

Predicting the causative pathogen among children with pneumonia using a causal Bayesian network.

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.

Modeling COVID-19 disease processes by remote elicitation of causal Bayesian networks from medical experts.

BACKGROUND: COVID-19 is a new multi-organ disease causing considerable worldwide morbidity and mortality. While many recognized pathophysiological mechanisms are involved, their exact causal relationships remain opaque. Better understanding is needed for predicting their progression, targeting therapeutic approaches, and improving patient outcomes. While many mathematical causal models describe COVID-19 epidemiology, none have described its pathophysiology. METHODS: In early 2020, we began developing such causal models. The SARS-CoV-2 virus's rapid and extensive spread made this particularly difficult: no large patient datasets were publicly available; the medical literature was flooded with sometimes conflicting pre-review reports; and clinicians in many countries had little time for academic consultations. We used Bayesian network (BN) models, which provide powerful calculation tools and directed acyclic graphs (DAGs) as comprehensible causal maps. Hence, they can incorporate both expert opinion and numerical data, and produce explainable, updatable results. To obtain the DAGs, we used extensive expert elicitation (exploiting Australia's exceptionally low COVID-19 burden) in structured online sessions. Groups of clinical and other specialists were enlisted to filter, interpret and discuss the literature and develop a current consensus. We encouraged inclusion of theoretically salient latent (unobservable) variables, likely mechanisms by extrapolation from other diseases, and documented supporting literature while noting controversies. Our method was iterative and incremental: systematically refining and validating the group output using one-on-one follow-up meetings with original and new experts. 35 experts contributed 126 hours face-to-face, and could review our products. RESULTS: We present two key models, for the initial infection of the respiratory tract and the possible progression to complications, as causal DAGs and BNs with corresponding verbal descriptions, dictionaries and sources. These are the first published causal models of COVID-19 pathophysiology. CONCLUSIONS: Our method demonstrates an improved procedure for developing BNs via expert elicitation, which other teams can implement to model emergent complex phenomena. Our results have three anticipated applications: (i) freely disseminating updatable expert knowledge; (ii) guiding design and analysis of observational and clinical studies; (iii) developing and validating automated tools for causal reasoning and decision support. We are developing such tools for the initial diagnosis, resource management, and prognosis of COVID-19, parameterized using the ISARIC and LEOSS databases.

The Impact of a Multifaceted Tertiary Pediatric Hospital's Antimicrobial Stewardship Service.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Assessing the utility of routine viral surveillance performed in children undergoing autologous stem cell transplantation at a single centre.

We assessed the utility of routine viral surveillance for cytomegalovirus, Epstein-Barr virus and human adenovirus in children <16 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.

Urinary tract infections in children: building a causal model-based decision support tool for diagnosis with domain knowledge and prospective data.

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.

McConnell's Sign Is Not Always Pulmonary Embolism: The Importance of Right Ventricular Ischemia.

McConnell's sign is a well-established, specific echocardiographic sign for acute pulmonary embolism. Multiple theories have been proposed regarding the mechanism of McConnell's sign in the context of acute pulmonary embolism. Here, we present 2 patient cases in which McConnell's sign was seen with right ventricular ischemia without pulmonary embolism. (Level of Difficulty: Beginner.).

Infectious complications and optimising infection prevention for children with cochlear implants.

AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Standardised treatment and monitoring protocol to assess safety and tolerability of bacteriophage therapy for adult and paediatric patients (STAMP study): protocol for an open-label, single-arm trial.

INTRODUCTION: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy. METHODS AND ANALYSIS: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia's Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50-100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics. ETHICS AND DISSEMINATION: Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children's Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/). TRIAL REGISTRATION NUMBER: Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).

Viridans Group Streptococci in Pediatric Leukemia and Stem Cell Transplant: Review of a Risk-stratified Guideline for Empiric Vancomycin in Febrile Neutropenia.

Viridans group streptococci (VGS) are an important cause of sepsis in immunosuppressed children. We reviewed the effectiveness of risk-stratified addition of vancomycin to empiric febrile neutropenia therapy among 107 children with leukemia or undergoing an allogeneic transplant. Of 19 VGS bacteremia episodes, 78.9% were susceptible to risk-stratified antibiotics including 100% from high-risk patients. All blood cultures were flagged positive within 24 hours.