Comparison of Anti-Hepatitis A Antibody Pharmacokinetics in Healthy Australian Subjects Receiving Standard or Weight-Based Dosing of Polyvalent Immunoglobulin.

This randomized controlled trial compared two dosing regimens of the polyvalent immunoglobulin available for hepatitis A post-exposure prophylaxis in Australia. Participants were randomized to receive either 270 IU (standard dose) or 3.375 IU/kg (dose by weight).

Defining the phylogenetics and resistome of the major ribotypes circulating in Australia.

infection (CDI) remains a significant public health threat globally. New interventions to treat CDI rely on an understanding of the evolution and epidemiology of circulating strains. Here we provide longitudinal genomic data on strain diversity, transmission dynamics and antimicrobial resistance (AMR) of ribotypes (RTs) 014/020 (=169), 002 (=77) and 056 (=36), the three most prominent strains causing CDI in Australia.

Primer Part 1 - Preparing a laboratory quality improvement project.

Quality in laboratory medicine encompasses multiple components related to total quality management, including quality control (QC), quality assurance (QA), quality indicators, and quality improvement (QI). Together, they contribute to minimizing errors (pre-analytical, analytical, or post-analytical) in clinical service delivery and improving process appropriateness and efficiency. In contrast to static quality benchmarks (QC, QA, quality indicators), the QI paradigm is a continuous approach to systemic process improvement for optimizing patient safety, timeliness, effectiveness, and efficiency.

Performance evaluation of InfectID-BSI: A rapid quantitative PCR assay for detecting sepsis-associated organisms directly from whole blood.

Background: Bloodstream infections (BSIs) (presence of pathogenic organism in blood) that progress to sepsis (life-threatening organ dysfunction caused by the body's dysregulated response to an infection) is a major healthcare issue globally with close to 50 million cases annually and 11 million sepsis-related deaths, representing about 20% of all global deaths. A rapid diagnostic assay with accurate pathogen identification has the potential to improve antibiotic stewardship and clinical outcomes.

Methods: The InfectID-Bloodstream Infection (InfectID-BSI) test is a real-time quantitative PCR assay, which detects 26 of the most prevalent BSI-causing pathogens (bacteria and yeast) directly from blood (without need for pre-culture).

Self care and wellbeing in the face of COVID-19: Multidisciplinary perspectives and interprofessional experiences.

The human toll which has resulted from the coronavirus disease 2019 pandemic is clearly recognised. No single event in recent times has had such profound effects on health services and their staff wellbeing around the world. Policy making has been led by the requirement for confinement and surveillance to limit spread of the disease, and in clinical settings the impact of the necessity for the use of personal protective measures has caused huge strains on practice clinically and professionally.

Limited evidence of patient-to-patient transmission of Staphylococcus aureus strains between children with cystic fibrosis, Queensland, Australia.

Objectives: Here we used whole genome sequencing (WGS) to understand strain diversity and potential for patient-to-patient transmission of Staphylococcus aureus among children with cystic fibrosis (CF) in Queensland, Australia.

Methods: S. aureus isolates (n = 401) collected between January 2018 and April 2019 from 184 patients with CF (n = 318 isolates) and 76 patients without CF (n = 83 isolates) were subjected to WGS and subsequent multilocus sequence typing (MLST), and a phylogeny was constructed from core genome single nucleotide polymorphism (SNP) analysis.

Deep intronic variant in MVK as a cause for mevalonic aciduria initially presenting as non-syndromic retinitis pigmentosa.

Non-syndromic retinitis pigmentosa (NSRP) is a clinically and genetically heterogeneous group of disorders characterized by progressive degeneration of the rod and cone photoreceptors, often leading to blindness. The evolving association of syndromic genes to cause NSRP and the increasing role of intronic variants in explaining missing heritability in genetic disorders present challenges in establishing conclusive clinical and genetic diagnoses. This study sought to identify and validate the causative genetic variant(s) in a 13-year-old male initially diagnosed with NSRP.

Two Treponema pallidum strains account for the majority of syphilis infections, including among females, in Queensland, Australia.

An ongoing outbreak of syphilis in Australia, first reported in the state of Queensland in 2011, has led to increasing cases of congenital syphilis, including several deaths. Here, we applied multi-locus sequence typing (MLST) on available Treponema pallidum PCR-positive samples from the state of Queensland from the beginning of the outbreak to July 2020. In total, 393 samples from 337 males and 56 females were genotyped.

Human T-cell leukaemia virus type 1 and Adult T-cell leukaemia/lymphoma in Queensland, Australia: a retrospective cross-sectional study.

Objectives: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options.

Antibiotic resistance in uropathogens across northern Australia 2007-20 and impact on treatment guidelines.

Background: Urinary tract infections are common and are increasingly resistant to antibiotic therapy. Northern Australia is a sparsely populated region with limited access to healthcare, a relatively high burden of disease, a substantial regional and remote population, and high rates of antibiotic resistance in skin pathogens.

Objectives: To explore trends in antibiotic resistance for common uropathogens and in northern Australia, and how these relate to current treatment guidelines in the community and hospital settings.

Occurrence of Amyotrophic Lateral Sclerosis in Type 1 Gaucher Disease.

Objective: To report the association between type 1 Gaucher disease (GD1) and amyotrophic lateral sclerosis (ALS) in 3 unrelated families and to explore whether variants influence the risk of ALS.

Methods: We conducted retrospective chart reviews of patients with GD1 or their family members diagnosed with ALS. To further investigate whether there is an association between ALS and GD, we performed exploratory analyses for the presence of variants in 3 ALS cohorts from Toronto (Canada), Montreal (Canada), and Project MinE (international), totaling 4,653 patients with ALS and 1,832 controls.

Rapid macrolide and amikacin resistance testing for in people with cystic fibrosis.

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.

Antimicrobial resistance surveillance of Clostridioides difficile in Australia, 2015-18.

Background: Clostridioides difficile was listed as an urgent antimicrobial resistance (AMR) threat in a report by the CDC in 2019. AMR drives the evolution of C. difficile and facilitates its emergence and spread.

Genomic surveillance, characterization and intervention of a polymicrobial multidrug-resistant outbreak in critical care.

Infections caused by carbapenem-resistant (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole-genome sequencing (WGS) response to a persistent CR-Ab outbreak in a Brisbane hospital between 2016-2018..

Mycoplasma genitalium infections can comprise a mixture of both fluoroquinolone-susceptible and fluoroquinolone-resistant strains.

Background: Mycoplasma genitalium was recently added to the CDC's antimicrobial resistance threats 'watch list', as it has rapidly become resistant to mainstay treatments. In Australia, treatment failure with fluoroquinolones remain commonplace, even when Sanger sequencing fails to identify evidence of resistance mutations.

Methods: Suspecting that Sanger sequencing may miss low-load mixed infections, we applied three additional PCR-based approaches (allele-specific primer-based PCR, probe-based PCR and amplicon deep sequencing) to detect mutations associated with fluoroquinolone susceptibility/resistance.

Phenotypic and Genotypic Spectrum of Glucose Transporter-1 Deficiency Syndrome.

Background: Glucose Transporter-1 (GLUT1) Deficiency Syndrome (GLUT1DS) is caused by defective transport of glucose across the blood-brain barrier into brain cells resulting in hypoglycorrhachia due to the heterozygous pathogenic variants in SLC2A1. We report on the phenotypic spectrum of patients with pediatric GLUT1DS as well as their diagnostic methods from a single center in Canada.

Methods: We reviewed patient charts for clinical features, biochemical and molecular genetic investigations, neuroimaging, treatment modalities, and outcomes of patients with GLUT1DS at our institution.

Evidence for an increase in the intensity of inter-seasonal influenza, Queensland, Australia, 2009-2019.

Background: Inter-seasonal influenza cases have been increasing in Australia. Studies of influenza seasonality typically focus on seasonal transmission in temperate regions, leaving our understanding of inter-seasonal epidemiology limited. We aimed to improve understanding of influenza epidemiology during inter-seasonal periods across climate zones, and explored influenza intensity and strain dominance patterns over time.

De Novo variants in EEF2 cause a neurodevelopmental disorder with benign external hydrocephalus.

Eukaryotic translation elongation factor 2 (eEF2) is a key regulatory factor in gene expression that catalyzes the elongation stage of translation. A functionally impaired eEF2, due to a heterozygous missense variant in the EEF2 gene, was previously reported in one family with spinocerebellar ataxia-26 (SCA26), an autosomal dominant adult-onset pure cerebellar ataxia. Clinical exome sequencing identified de novo EEF2 variants in three unrelated children presenting with a neurodevelopmental disorder (NDD).

Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.

Introduction: This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial.

Methods: Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders.

Laboratory-Based Surveillance of Clostridium difficile Infection in Australian Health Care and Community Settings, 2013 to 2018.

In the early 2000s, a binary toxin (CDT)-producing strain of , ribotype 027 (RT027), caused extensive outbreaks of diarrheal disease in North America and Europe. This strain has not become established in Australia, and there is a markedly different repertoire of circulating strains there compared to other regions of the world. The Antimicrobial Resistance Surveillance (CDARS) study is a nationwide longitudinal surveillance study of infection (CDI) in Australia.

Fatal Respiratory Diphtheria Caused by ß-Lactam-Resistant Corynebacterium diphtheriae.

Background: Diphtheria is a potentially fatal respiratory disease caused by toxigenic Corynebacterium diphtheriae. Although resistance to erythromycin has been recognized, β-lactam resistance in toxigenic diphtheria has not been described. Here, we report a case of fatal respiratory diphtheria caused by toxigenic C.