Pediatric Hepatitis and Respiratory Viruses: A Spatiotemporal Ecologic Analysis.

INTRODUCTION: Beginning in early 2022, clusters of severe pediatric hepatitis were reported in Europe and the United States. To date, no cause has been identified although human adenovirus 41 has been proposed in a proportion of cases. We examined population data >11 years for hepatitis clusters in Victoria, Australia, and whether any were spatiotemporally associated with community transmission of common respiratory viruses. METHODS: We used SaTScan to analyze for clusters of pediatric hepatitis and respiratory adenoviruses in Victoria. Negative binomial regression analysis was performed to determine any associations between hepatitis and respiratory viruses across Victoria between July 1, 2011, and June 30, 2022. RESULTS: A number of positive associations were observed in Victoria between pediatric hepatitis clusters and respiratory viruses in our spatiotemporal analysis. A positive association was not found with respiratory adenoviruses or SARS-CoV-2. Increased hepatitis clusters were observed in 2021 and 2022 as noted internationally. CONCLUSION: The current hepatitis outbreak is novel and, although respiratory viruses are broadly associated with hepatitis, SARS-CoV-2 and respiratory adenoviruses are unlikely to be related.

Guillain-Barré syndrome temporally associated with COVID-19 vaccines in Victoria, Australia.

Guillain-Barré syndrome (GBS) is an adverse event of special interest (AESI) for surveillance systems monitoring adverse events following immunisation (AEFI) with COVID-19 vaccines. Emerging data support a temporal association between GBS and adenovirus-vector COVID-19 vaccines. We present a case series of GBS reports submitted between February and November 2021 to our enhanced spontaneous surveillance system (SAEFVIC) in Victoria, Australia, following vaccination with either the adenovirus-vector vaccine Vaxzevria ChadOx1-S (AstraZeneca) or an mRNA vaccine (Comirnaty BNT162b2 [Pfizer-BioNTech] or Spikevax mRNA-1273 [Moderna]). For each report, Brighton Collaboration case definitions were used to describe diagnostic certainty. Severity was graded using the GBS Disability Score. The observed incidence of GBS following immunisation against COVID-19 was compared to expected background ICD10-AM G61.0 coded hospitalisations. There were 41 total cases of GBS reported to SAEFVIC following Vaxzevria (n = 38), Comirnaty (n = 3), or Spikevax (n = 0) vaccines. The observed GBS incidence rate exceeded the expected background rate for Vaxzevria only, with 1.85 reports per 100,000 doses following dose 1, higher than the expected rate of 0.39 hospital admissions per 100,000 adults within 42 days of vaccination. Of 38 GBS reports following Vaxzevria, the median age at vaccination was 66 years and median onset of symptoms was 14 days following immunisation. There was one death. Four cases initially categorised as GBS were later reclassified as acute-onset chronic inflammatory demyelinating polyneuropathy. Fatigue was the predominant persisting symptom reported at follow up. Additional global studies are required to characterise risk factors, clinical variability, and to provide precision and generalizability regarding AEFI risks such as GBS associated with different vaccine platforms, which will help inform communication of the potential benefits and risks of COVID19 vaccination.

Characteristics, management and changing incidence of children with empyema in a paediatric intensive care unit.

AIM: Paediatric intensive care unit (PICU) admissions for empyema increased following the 13-valent pneumococcal conjugate vaccine (PCV13). We describe the clinical characteristics, management and outcomes for children with empyema and compare incidence before and after PCV13. METHODS: Retrospective study of patients <18 years admitted to The Royal Children's Hospital Melbourne PICU with empyema between January 2016 and July 2019. We investigated the incidence of empyema during two time periods: 2007-2010 (pre-PCV13) and 2016-2019 (post-PCV13). RESULTS: Seventy-one children (1.9% of all PICU admissions) were admitted to PICU with empyema between 2016 and 2019. Sixty-one (86%) had unilateral disease, 11 (16%) presented with shock and 44 (62%) were ventilated. Streptococcus pneumoniae and group A Streptococcus were the most commonly identified pathogens. Forty-five (63%) were managed with video-assisted thoracoscopic surgery (VATS). There was a 31% reduction in empyema hospitalisations as a proportion of all hospitalisations (IRR 0.69, 95% CI 0.59-0.8), but a 2.8-fold increase in empyema PICU admissions as a proportion of all PICU admissions (95% CI 2.2-3.5, P < 0.001). For the PICU cohort, this was accompanied by reduction in PIM2 probability of death (median 1% vs. 1.9%, P = 0.02) and duration of intubation (median 69 h vs. 126.5 h, P = 0.045). CONCLUSIONS: In children with empyema in PICU 62% required ventilation, 16% had features of shock and 63% received VATS. Empyema admissions, as a proportion of all PICU admissions, increased in the era post-PCV13 compared to pre-PCV13 despite no increase in illness severity at admission.

Rare Infant Case of Pulmonary Aspergilloma Highlighting Common Challenges With Voriconazole Dosing.

We describe a 6-week-old male-term infant with a pulmonary aspergilloma diagnosed following lobectomy for suspected pleuropulmonary blastoma, with characteristic histopathologic findings and Aspergillus detected by polymerase chain reaction. Intensive testing did not reveal primary or secondary immunodeficiency. During 5 weeks treatment with voriconazole including regular therapeutic drug monitoring and dose adjustment, a level in the target range was never achieved. When the patient developed photosensitivity, treatment was stopped without relapse over 12 months follow-up. Voriconazole dosing is notoriously challenging in children. We review the cumulative published experience with voriconazole use in infants to highlight even greater difficulty in infants. Pulmonary aspergillosis is typically a disease affecting immunocompromised or critically ill patients. In children, it is well described in those with chronic granulomatous disease (CGD) as a complication of immunosuppressive antineoplastic chemotherapy and rarely in extremely- or very-low birthweight premature neonatal intensive care patients. The diagnosis is extremely rare in children without underlying risk factors. To our knowledge, this is the first report of a pulmonary aspergilloma in an immunocompetent infant.

Congenital Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis.

We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.

Australia-wide point prevalence survey of the use and appropriateness of antimicrobial prescribing for children in hospital.

OBJECTIVES: To describe antimicrobial use in hospitalised Australian children and to analyse the appropriateness of this antimicrobial use. DESIGN: Multicentre single-day hospital-wide point prevalence survey, conducted in conjunction with the Antimicrobial Resistance and Prescribing in European Children study. SETTING: Eight children's hospitals across five Australian states, surveyed during late spring and early summer 2012. PATIENTS: Children and adolescents who were inpatients at 8 am on the day of the survey. MAIN OUTCOME MEASURES: Quantity and quality of antimicrobial prescribing. RESULTS: 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]), ß-lactam-ß-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. CONCLUSION: 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.