Infectious Diseases - Research Publications

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    Phenotypic distribution and tolerability of re-vaccination in individuals with delayed hypersensitivity to COVID-19 vaccines
    De Luca, J ; Awad, A ; Vogrin, S ; Waldron, J ; Douglas, A ; Chua, K ; Holmes, N ; Trubiano, J (MOSBY-ELSEVIER, 2023-02)
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    The Who, What, When, and Where of Inpatient Direct Oral Penicillin Challenge-Implications for Health Services Implementation
    Trubiano, JA ; Vogrin, S ; Mitri, E ; Hall, R ; Copaescu, A ; Waldron, J ; De Luca, J ; Rose, M ; Mackay, G ; Lambros, B ; Douglas, AP ; Holmes, NE ; Chua, KYL (OXFORD UNIV PRESS INC, 2023-07-05)
    Inpatient direct oral challenge programs are increasingly deployed as part of antimicrobial stewardship initiatives to reduce the burden and impacts of penicillin allergy labels on antibiotic prescribing. Using data from a prospective, multicenter cohort inpatient penicillin allergy program, we identify the key targets for delabeling to aid health service implementation.
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    Study protocol: Australasian Registry of Severe Cutaneous Adverse Reactions (AUS-SCAR)
    James, F ; Goh, MSY ; Mouhtouris, E ; Vogrin, S ; Chua, KYL ; Holmes, NE ; Awad, A ; Copaescu, A-M ; De Luca, JF ; Zubrinich, C ; Gin, D ; Cleland, H ; Douglas, A ; Kern, JS ; Katelaris, CH ; Thien, F ; Barnes, S ; Yun, J ; Tong, W ; Smith, WB ; Carr, A ; Anderson, T ; Legg, A ; Bourke, J ; Mackay, LK ; Aung, AK ; Phillips, EJ ; Trubiano, J (BMJ PUBLISHING GROUP, 2022-08)
    INTRODUCTION: Severe cutaneous adverse reactions (SCAR) are a group of T cell-mediated hypersensitivities associated with significant morbidity, mortality and hospital costs. Clinical phenotypes include Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP). In this Australasian, multicentre, prospective registry, we plan to examine the clinical presentation, drug causality, genomic predictors, potential diagnostic approaches, treatments and long-term outcomes of SCAR in Australia and New Zealand. METHODS AND ANALYSIS: Adult and adolescent patients with SCAR including SJS, TEN, DRESS, AGEP and another T cell-mediated hypersensitivity, generalised bullous fixed drug eruption, will be prospectively recruited. A waiver of consent has been granted for some sites to retrospectively include cases which result in early mortality. DNA will be collected for all prospective cases. Blood, blister fluid and skin biopsy sampling is optional and subject to patient consent and site capacity. To develop culprit drug identification and prevention, genomic testing will be performed to confirm human leukocyte antigen (HLA) type and ex vivo testing will be performed via interferon-γ release enzyme linked immunospot assay using collected peripheral blood mononuclear cells. The long-term outcomes of SCAR will be investigated with a 12-month quality of life survey and examination of prescribing and mortality data. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Austin Health Human Research Ethics Committee (HREC/50791/Austin-19). Results will be published in peer-reviewed journals and presented at relevant conferences. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12619000241134).
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    Victorian Specialist Immunisation Services (VicSIS) - bolstering adult clinics for COVID-19 vaccines
    Gordon, SF ; Virah Sawmy, E ; Duckworth, E ; Wolthuizen, M ; Clothier, HJ ; Chea, M ; Tenneti, N ; Blow, N ; Buttery, JP ; de Luca, J ; Korman, TM ; Barnes, S ; Slade, C ; Maggs, C ; Giles, ML ; Teh, BW ; Aboltins, C ; Langan, KM ; Van Diemen, A ; Crawford, NW (TAYLOR & FRANCIS INC, 2022-11-30)
    The Victorian Specialist Immunization Services (VicSIS) was established in Victoria, Australia, in February 2021, aiming to enhance vaccine safety services for Coronavirus disease (COVID-19) vaccines. VicSIS supports practitioners and patients with complex vaccine safety questions, including those who experience adverse events following immunization (AEFI) after COVID-19 vaccines. VicSIS provides individual vaccination recommendations, allergy testing, vaccine challenges, and vaccination under supervision. VicSIS initially comprised of eight adult COVID-19 specialist vaccination clinics, subsequently, expanding to better support pediatric patients as the Australian vaccine roll-out extended to adolescents and children. Since their establishment to September 2021, the inaugural VicSIS clinics received a total of 26,401 referrals and reviewed 6,079 patients. Consults were initially predominantly for pre-vaccination reviews, later predominantly becoming post-vaccination AEFI reviews as the program progressed. Regardless of the type of consult, the most common consult outcome was a recommendation for routine vaccination (73% and 55% of consult outcomes respectively). VicSIS is an integral component of the COVID-19 vaccination program and supports confidence in COVID-19 vaccine safety by providing consistent advice across the state. VicSIS aims to strengthen the health system through the pandemic, bolstering specialist immunization services beyond COVID-19 vaccines, including training the next generation of vaccinology experts.
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    Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults
    Slade, CA ; Bosco, JJ ; Giang, TB ; Kruse, E ; Stirling, RG ; Cameron, PU ; Hore-Lacy, F ; Sutherland, MF ; Barnes, SL ; Holdsworth, S ; Ojaimi, S ; Unglik, GA ; De Luca, J ; Patel, M ; McComish, J ; Spriggs, K ; Tran, Y ; Auyeung, P ; Nicholls, K ; O'Hehir, RE ; Hodgkin, PD ; Douglass, JA ; Bryant, VL ; van Zelm, MC (FRONTIERS MEDIA SA, 2018-05-14)
    BACKGROUND: Predominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy. OBJECTIVES: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. METHODS: We identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features. RESULTS: 179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16-87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort. CONCLUSION: Our data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.