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Background Although common, antimicrobial allergy labels (AAL) rarely reflect immunologically-mediated hypersensitivity and can lead to poorer outcomes from alternative antimicrobial agents. Antimicrobial stewardship programs are ideally placed to assess AAL early as a means of improving antimicrobial use. Objectives To quantify the prevalence of AAL in patients referred for antimicrobial stewardship review and assess their impact on antibiotic prescribing, patient mortality, hospital length of stay, readmission, and rates of multidrug-resistant infections. Methods We conducted a retrospective analysis of adult patients referred for inpatient antimicrobial prospective audit and feedback rounds (PAFR) via an electronic referral system (eReferrals) over a 12-month period in 2015. Outcome data was collected for a period of 36 months following the initial review. Results Of the 639 patient records reviewed, 630 met inclusion criteria; 103 (16%) had an AAL, of which 82 (13%) had reported allergies to β-lactam antibiotics. Those with AAL were significantly less likely to be receiving guideline-recommended antimicrobial therapy (50% versus 64%, p=0.0311), however there were no significant difference in mortality, hospital length of stay, readmission or increased incidence of multidrug-resistant infections. Conclusions Our cohort demonstrated that AAL was associated with reduced adherence to antibiotic guidelines. The lack of association with adverse outcomes may reflect limitations within the study including retrospective cohort study numbers and observational nature, further skewed by high rates of poor documentation. A clear opportunity exists for antimicrobial stewardship programs to incorporate allergy assessment, delabelling, challenge and referral into these rounds. This article is protected by copyright. All rights reserved.

There is substantive and accumulating evidence that endemic exposure to plastic-associated chemicals (PACs) contribute to the pathophysiology of metabolic conditions, like obesity, diabetes, and heart disease. The consequences of this endemic exposure in inducing a pro-inflammatory state in adipose tissues as a critical link between exposure and disease is reviewed.In general, PACs are classified as nonpersistent in vivo because of their rapid metabolism to easily excreted forms. The parental chemicals, however, are typically lipophilic, with the potential to bioaccumulate. Recent data from selected association studies suggest exposure to PACs drive predisease states like obesity and inflammation of the adipose tissues. A range of experimental studies are discussed with a focus on biological mechanisms that are susceptible to the influence of PACs and which may promote metabolic disease, the detection of PACs within susceptible tissues and biological effects that are detectable at doses that correspond to real-life exposures to these chemicals.If we hypothesize the toxic pressure from chronic exposure to PACs will progress disease processes, then individuals with comprehensively characterized indicators of premetabolic disease could undergo trials of quantifiable interventions to reduce exposure to PACs to test if the trajectory of disease-associated analytes, is altered.

Background Unnecessary antibiotic avoidance due to allergy fears has adverse cost and health implications however, the problem is difficult to resolve because patient and provider-related factors leading to avoidance are multifactorial. The perspectives of patients can be explored using qualitative research methods to reach the heart of the problem. Objective To reveal factors leading patients to report antibiotic allergy, and determine what education is required to prevent the cycle of erroneous allergy reporting. Methods The 29 patients were a sample of convenience recruited from a tertiary public hospital in Western Australia; 18 were inpatients and 11 outpatients, with a median age of 64.2 years, and 15 (55%) were female. Semi-structured interviews assessed patients’ understanding and knowledge of three topics: (1) antibiotic allergy, (2) antibiotic allergy testing, and (3) outcomes of testing. Interview transcripts underwent thematic analysis by two researchers, independently. Results Three overlapping themes emerged as influential across topics: (1) Severity of the Index Reaction, (2) Trust in family and health care providers, and (3) Health literacy. Patients were largely unaware of the benefits of confirmatory testing, and the detrimental health consequences of unnecessary avoidance. Patients displayed trust in health care providers’ expertise, and assumed that medical records were accurate to prevent prescribing errors. Conclusions The findings provide evidence for an effective patient education strategy, and highlight failures among hospital and primary health providers to recognise the potential harm of unverified antibiotic allergy. Healthcare professionals are influential at multiple steps of a patient’s healthcare journey and addressing unconfirmed antibiotic allergy should be taken at each opportunity.

During solid organ transplantation, donor leukocytes, including myeloid cells, are transferred within the organ to the recipient. Both tolerogenic and alloreactive roles have been attributed to donor myeloid cells; however, their subset-specific retention posttransplantation has not been investigated in detail.Major histocompatibility complex (MHC)-matched and mismatched liver transplants were performed in mice, and the fate of donor and recipient myeloid cells was assessed.Following MHC-matched transplantation, a proportion of donor myeloid cells was retained in the graft, whereas others egressed and persisted in the blood, spleen, and bone marrow but not the lymph nodes. In contrast, after MHC-mismatched transplantation, all donor myeloid cells, except Kupffer cells, were depleted. This depletion was caused by recipient T and B cells because all donor myeloid subsets were retained in MHC-mismatched grafts when recipients lacked T and B cells. Recipient myeloid cells rapidly infiltrated MHC-matched and, to a greater extent, MHC-mismatched liver grafts. MHC-mismatched grafts underwent a transient rejection episode on day 7, coinciding with a transition in macrophages to a regulatory phenotype, after which rejection resolved.Phenotypic and kinetic differences in the myeloid cell responses between MHC-matched and mismatched grafts were identified. A detailed understanding of the dynamics of immune responses to transplantation is critical to improving graft outcomes.

Tissue-resident memory T (TRM) cells are non-recirculating cells that exist throughout the body. Although TRM cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze TRM cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate TRM cell function, durability and malleability. We find that unequal responsiveness to TGFβ is a major driver of this diversity. Notably, dampened TGFβ signaling results in CD103- TRM cells with increased proliferative potential, enhanced function and reduced longevity compared with their TGFβ-responsive CD103+ TRM counterparts. Furthermore, whereas CD103- TRM cells readily modified their phenotype upon relocation, CD103+ TRM cells were comparatively resistant to transdifferentiation. Thus, despite common requirements for TRM cell development, tissue adaptation of these cells confers discrete functional properties such that TRM cells exist along a spectrum of differentiation potential that is governed by their local tissue microenvironment.

The development of experimental models of cardiac transplantation in animals has contributed to many advances in the fields of immunology and solid organ transplantation. While the heterotopic vascularized murine cardiac transplantation model was initially utilized in studies of graft rejection using combinations of mismatched inbred mouse strains, access to genetically modified strains and therapeutic modalities can provide powerful new preclinical insights. Fundamentally, the surgical methodology for this technique has not changed since its development, especially with respect to important factors such as aseptic technique, anesthesia, and analgesia, which make material impacts on postsurgical morbidity and mortality. Additionally, improvements in perioperative management are expected to provide improvements in both animal welfare and experimental outcomes. This paper reports upon a protocol developed in collaboration with a subject matter expert in veterinary anesthesia and describes the surgical technique with an emphasis on perioperative management. Additionally, we discuss the implications of these refinements and provide details on troubleshooting critical surgical steps for this procedure.

The diagnosis and management of patients with chronic rhinosinusitis (CRS) may vary between otolaryngologists and allergists. Moreover, the adherence of different practitioners to European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 guideline recommendations has not been previously ascertained in Asia-Pacific regions.Different specialists' perceptions and managements of CRS in Asia-Pacific regions were assessed in an attempt to gauge these practices against EPOS 2020 guidelines.A transregional, cross-sectional survey was conducted to assess otolaryngologists' and allergists' perceptions and managements of CRS with regard to diagnosis, management and adherence to EPOS 2020 guidelines.Sixteen physicians in Asia-Pacific regions responded to the questionnaire. A total of 71.4% of otolaryngologists preferred to diagnose CRS with a combination of positive nasal symptoms and nasal endoscopy plus sinus CT, whereas 22.2% of allergists took such criterion to diagnose CRS. Compared to allergists, otolaryngologists more often considered the endotype classification (85.8% versus 55.5%). For the preferred first-line treatment, in addition to intranasal corticosteroids recommended by all respondents, 66.7% of allergists preferred antihistamines, whereas 71.4% of otolaryngologists preferred nasal saline irrigation. Regarding the proper timing of surgery, 71.5% of otolaryngologists reported 8-12 weeks of treatment after the initiation of medication, while more than half of the allergists recommended 4-6 weeks of medical treatment.This survey shows that variable perceptions and practices for CRS may exist between physicians with different specialties and highlights the need for increased communication and awareness between otolaryngologists and allergists to improve the diagnosis and treatment of CRS.

Evidence of autoimmune disease associated with hepatitis C virus (HCV)-infection has important clinical implications. A systematic profile of these autoantibodies in relevant clinical cohorts relative to healthy controls is needed to better inform current standard of care for chronic hepatitis C. Samples from an Australian cohort of chronic HCV-infected subjects (n=127) were tested for the presence of 19 diagnostic autoantibodies and compared with data available from a control cohort representing a general Caucasian population (n=198). Chronic HCV-infected individuals had a greater number of autoantibodies than controls (p

Penicillin allergy accounts for the majority of all reported adverse drug reactions in adults and children. Foregoing first-line antibiotic therapy due to penicillin allergy label is associated with an increased prevalence of infections by resistant organisms and longer hospitalisation. Clinician awareness of allergy assessment, referral indications, management of allergy and anaphylaxis is therefore vital but globally lacking. We aim to assess the knowledge of penicillin allergy, assessment and management in Western Australian health professionals.An anonymous survey was distributed to pharmacists, nurses and physicians within Western Australian paediatric and adult Hospitals, Community and General Practice.In total, 487/611 were completed and included in the statistical analysis. Only 62% (301/487) of respondents routinely assessed for patient medication allergies. Of those who assessed allergy, 9% (28/301) of respondents met the Australian standards for allergy assessment. Only 22% (106/487) of participants correctly cited all indications for management with adrenaline in anaphylaxis to antibiotics and 67% (197/292) of physicians rarely or never referred to an allergy service. Paediatric clinicians had an increased understanding of allergy assessment and anaphylaxis management. Recent penicillin allergy education within a 5-year period led to significant improvements in allergy knowledge.Overall, knowledge, assessment and management of penicillin allergies among practitioners in Western Australia are currently inadequate in adults and paediatric clinicians to provide safe and effective clinical care. The implementation of a targeted education program for WA health professionals is urgently required and is expected to improve clinician knowledge and aid standardised penicillin assessment (de-labelling) practices.

The reported frequency and types of adverse events following initial vaccination and revaccination with Bacille Calmette-Guérin (BCG) varies worldwide. Using active surveillance in a randomised controlled trial of BCG vaccination (the BRACE trial), we determined the incidence and risk factors for the development of BCG injection site abscess and regional lymphadenopathy. Injection site abscess occurred in 3% of 1387 BCG-vaccinated participants; the majority (34/41, 83%) resolved without treatment. The rate was higher in BCG-revaccinated participants (OR 3.6, 95% CI 1.7–7.5), in whom abscess onset was also earlier (median 16 vs. 27 days, p = 0.008). No participant with an abscess had a positive interferon-gamma release assay. Regional lymphadenopathy occurred in 48/1387 (3%) of BCG-vaccinated participants, with a higher rate in revaccinated participants (OR 2.1, 95% CI 1.1–3.9). BCG-associated lymphadenopathy, but not injection site abscess, was influenced by age and sex. A previous positive tuberculin skin test was not associated with local reactions. The increased risk of injection site abscess or lymphadenopathy following BCG revaccination is relevant to BCG vaccination policy in an era when BCG is increasingly being considered for novel applications.

Background With the emergence of novel vaccines and new applications for older vaccines, co-administration is increasingly likely. The immunomodulatory effects of BCG could theoretically alter the reactogenicity of co-administered vaccines. Using active surveillance in a randomised controlled trial, we aimed to determine whether co-administration of BCG vaccination changes the safety profile of influenza vaccination. Methods Participants who received influenza vaccine alone (Influenza group) were compared with those who also received BCG-Denmark vaccine in the contralateral arm (Influenza+BCG group). Data on the influenza vaccination site were collected using serial questionnaires and active follow-up for 3 months post vaccination. Results Of 1351 participants in the Influenza+BCG group and 1418 participants in the Influenza group, 2615 (94%) provided influenza vaccine safety data. There was no significant difference in the proportion of participants with any local adverse reaction between the Influenza+BCG group and the Influenza group (918/1293 [71.0%] versus (906/1322 [68.5%], p = 0.17). The proportion of participants reporting any pain, erythema and tenderness at the influenza vaccination site were similar in both groups. Swelling was less frequent (81/1293 [6.3%] versus 119/1322 (9.0%), p = 0.01) and the maximal diameter of erythema was smaller (mean 1.8 cm [SD 2.0] versus 3.0 cm [SD 2.5], p Conclusions Adverse events following influenza vaccination are not increased when BCG is co-administered.

Childhood allergy is common, and increasing. Many children are incorrectly labeled as having allergy or adverse drug reactions. This can pose a dilemma for anesthetists and lead to a change in practice or drug selection. We review the pathophysiology of hypersensitivity reactions and the implications for anesthesia of food allergy, atopy, and family history of allergy in children. The epidemiology of anaphylaxis is discussed. We discuss the common triggers of perioperative anaphylaxis in children and explore emerging triggers including chlorhexidine and sugammadex. Accurate data on pediatric perioperative anaphylaxis is limited worldwide, with marked geographic variation. This highlights the need for accurate local, district and/or nationwide incident reporting. The clinical features, diagnosis, and management of anaphylaxis under anesthesia are discussed. We review the process of expert allergy testing following a suspected case of anaphylaxis to guide future safe anesthesia administration. The preoperative consultation is an opportunity for referral for allergy testing to allow de-labeling. This has the potential for improved antibiotic stewardship and more effective treatment with first-line therapeutic agents.

Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.

Background: Paracetamol is a widely used analgesic to which hypersensitivity reactions are rare. Reactions to paracetamol May be due to the pharmacological effects of cyclooxygenase-1 inhibition or, more rarely, due to a selective allergy against paracetamol. Objective: This article aims to review the current literature in the context of two cases seen in the authors' allergy practice. Discussion: Paracetamol allergy is uncommon and, as a result, May be overlooked as a cause for immediate hypersensitivity, which can lead to a significant delay in diagnosis. Currently, specialist referral for a supervised oral challenge is required for formal diagnosis.

Self-reported antibiotic allergies are common among hospitalized adults and children. However, there is a paucity of studies investigating the impact of an antibiotic allergy label in childhood.To investigate the impact of antibiotic allergy labeling on clinical outcomes in children.A retrospective study was conducted in a major pediatric tertiary hospital to capture inpatient admissions (N = 1672) in April 2014 and April 2015. Data, collected by chart review, included documented antibiotic allergy labels, antibiotic prescriptions, admitting specialty, hospital length of stay, and hospital readmissions.Of the 1672 pediatric patients surveyed, 58.1% were male and 44.8% were prescribed antibiotics. Antibiotic allergy labels were recorded in 5.3% of patients; most were β-lactam allergy labels (85%), mostly to unspecified penicillins. There was an increasing incidence of antibiotic allergy label with age, which was statistically significant (P.001); no sex effect was seen. Patients with antibiotic allergy labels received more macrolide (P = .045), quinolones (P = .01), lincosamide (P.001), and metronidazole (P = .009) antibiotics than did patients without an antibiotic allergy label. After adjusting for patient age, sex, principal diagnosis, and admitting specialty, children with any antibiotic or β-lactam allergy label had longer hospital stays (odds ratio, 1.62; 95% CI, 1.05-2.50; P = .03) with a mean length of hospital stay of 3.8 days for those without a label and 5.2 days for those with a β-lactam allergy label.This is the first study demonstrating the negative impact of antibiotic allergy labels on clinical outcomes in children, as evidenced by significant alternate antibiotic use and longer hospital stays.

We recently determined that allergy training programs have improved physician recognition and diagnosis of pediatric anaphylaxis in the last decade.To investigate for changes in management, in particular the appropriate use of adrenaline for the treatment of anaphylaxis in a tertiary pediatric emergency department (PED).We conducted a retrospective case note study including children aged 0 to 16 years coded and verified for anaphylaxis comparing cases in years 2003/2004 with 2012. This included standardized information on clinical presentation, demographic characteristics, vital signs, mode of transport, and management of anaphylaxis including the use of adrenaline and/or adjunct therapy. Follow-up management plans were also recorded.In 2003/2004, a total of 92 cases were coded and verified for anaphylaxis from 83,832 PED presentations compared with 159 cases from 71,822 PED presentations in 2012. A significantly higher proportion of cases were appropriately managed with adrenaline in 2012 compared with 2003/2004, when intensive training programs had not yet been introduced (P = .03). Vital signs were more frequently documented in 2012 (P.001) than in 2003/2004, and there was significantly less administration of other medications (corticosteroids, bronchodilators, and antihistamines) (P.05). Also, changes in discharge management occurred with an improved dispensing/prescription of adrenaline autoinjectors and more frequent follow-up arrangement with specialist allergy services (P.001).There was a significant improvement in the management of anaphylaxis over this 10-year period. This change was observed after the introduction of intensified physician training programs in which anaphylaxis management was a key component highlighting the importance of cooperation between pediatric emergency and allergy services.

Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same period, and chronic rejection remains a major cause of graft failure. The importance of donor, or "passenger," lymphocytes to the induction of tolerance to allografts was recognized in the 1990s, but their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described. These lymphocytes include tissue-resident memory T cells, regulatory T cells, γδ T cells, invariant natural killer T cells, and innate lymphoid cells. These cells reside in commonly transplanted solid organs, including the liver, kidneys, heart, and lung; however, their contribution to graft acceptance or rejection has not been examined in detail. Similarly, it is unclear whether tissue-resident cells derived from the pool of recipient-derived lymphocytes play a specific role in transplantation biology. This review summarizes the evidence for the roles of tissue-resident lymphocytes in transplant immunology, focussing on their features, functions, and relevance for solid organ transplantation, with specific reference to liver, kidney, heart, and lung transplantation.

Summary Alterations to organ biology caused by transplantation can have major impacts on the outcome. Tissue-resident lymphocytes normally maintain an organ’s immunity and function and are transferred during transplantation. Here, we provide a detailed protocol for the isolation of leukocytes, including tissue-resident lymphocytes, from transplanted livers and hearts in mice. Phenotypic and functional analysis of conventional and unconventional T cells by flow cytometry is included. This protocol can also be used for the effective isolation of leukocytes from non-transplanted livers and hearts. For complete details on the use and execution of this protocol, please refer to Prosser et al. (2021) .

Non-immediate allergic cutaneous reactions to heparins have been increasingly reported, typically manifesting as large, eczematous plaques at sites of subcutaneous injection. Patients may demonstrate cross-reactivity between unfractionated heparin, low molecular weight heparin and semi-synthetic heparinoids, making finding an alternative difficult. Fondaparinux has been identified as a useful alternative in such patients; here we present the first two documented cases in Australia and a literature review.

Tissue integrity and repair is assisted by tissue-resident leukocytes, which also provide immediate responses to infection. It is unclear to what extent tissue-resident cells are perturbed following solid organ transplantation. For the first time, we report on the varied fates of 13 subsets of B, T and ILC lymphocytes after murine liver and heart transplantation in the absence of tissue mismatch and immunosuppression . Strikingly, donor-derived unconventional lymphocytes are predominantly maintained in livers, but not hearts, as long-term tissue-resident and self-renewing populations. In contrast, donor conventional lymphocytes are rapidly displaced by recipient populations, but this does not occur in the absence of recipient T and B cells. Overall, infiltrating recipient cells fail to recreate the native organ’s phenotypically diverse tissue-resident lymphocyte composition. These changes in post-transplant immunity are likely to leave the graft vulnerable to infection and impair long-term graft function.

The lung achieves an efficient gas exchange between a complex non‐sterile atmosphere and the body via a delicate and extensive epithelial surface, with high efficiency because of elastic deformation allowing for an increase and decrease in volume during the process of breathing and because of an extensive vasculature which aids rapid gas diffusion. The lungs’ large surface area exposes the organ to a continual risk of damage from pathogens, toxins or irritants; however, lung damage can be rapidly healed via regenerative processes that restore its structure and function. In response to sustained and extensive damage, the lung is healed via a non‐regenerative process resulting in scar tissue which locally stiffens its structure, which over time leads to a serious loss of lung function and to increasing morbidities. This review discusses what is known about the factors which influence whether a lung is healed by regeneration or repair and what potential new therapeutic approaches may positively influence lung healing., This review discusses what is known about the detection, response and resolution of lung damage and what might influence whether a lung is healed by regeneration or repair. It also presents potential therapeutic approaches that may positively influence lung healing.

Objectives The epidemiology, clinical characteristics and outcomes of antimicrobial-associated anaphylaxis remain ill-defined. We sought to examine antimicrobial anaphylaxis with regard to: (i) the frequency of implicated antimicrobials; (ii) attributable mortality; and (iii) referral for definitive allergy assessment. Methods This was conducted through a national retrospective multicentre cohort study at five Australian tertiary hospitals (January 2010 to December 2015). Cases of antimicrobial anaphylaxis were identified from ICD-10 coding and adverse drug reaction committee databases. Results There were 293 participants meeting the case definition of antimicrobial anaphylaxis and 310 antimicrobial anaphylaxis episodes. Of 336 implicated antimicrobials, aminopenicillins (62/336, 18.5%) and aminocephalosporins (57/336, 17%) were implicated most frequently. ICU admission occurred in 43/310 (13.9%) episodes; however, attributable mortality was low (3/310, 1%). The rate of anaphylaxis to IV antibiotics was 3.5 (95% CI = 2.9–4.3) per 100 000 DDDs and the rate of hospital-acquired anaphylaxis was 1.9 (95% CI = 2.1–3.3) per 100 000 occupied bed-days. We observed overall low rates of hospital discharge documentation (222/310, 71.6%) and follow-up by specialist allergy services (73/310, 23.5%), which may compromise medication safety and antimicrobial prescribing in future. Conclusions This study demonstrated that a high proportion of severe immediate hypersensitivity reactions presenting or acquired in Australian hospitals are secondary to aminopenicillins and aminocephalosporins. Overall rates of hospital-acquired anaphylaxis, predominantly secondary to cephalosporins, are low, and also associated with low inpatient mortality.

Because of the relatively high prevalence of both hepatitis B infection and various forms of autoimmune inflammatory diseases treated with aggressive immunotherapy, reactivation of hepatitis B occurs in a substantial number of patients. The risk of reactivation depends on the degree and duration of immunosuppression. A large number of drug treatments have resulted in reactivation of hepatitis B virus infection and, based on the mechanisms and extent of immunosuppression, recommendations for some of the newer classes of immunosuppressive drugs are provided.

Patients with malignancies require chemotherapy and other immunosuppressive therapies for treatment. Because of this immunosuppression, in patients who have ever been exposed to hepatitis B it is possible for reactivation to occur. This reactivation can be fatal. Reactivation is particularly likely in patients who receive B cell-active agents such as rituximab. The occurrence of reactivation flares may also delay further chemotherapy, which can negatively affect the outcome of the underlying malignancy. Accordingly, it is important to screen patients for markers of hepatitis B and institute antiviral prophylaxis to prevent reactivation.

Current recommendations concerning hepatitis C virus (HBV) reactivation are limited, with nearly all guidelines focused on its occurrence in patients with hematological malignancies or some solid tumors, who are treated with immunosuppressive therapies. Few of the guidelines address reactivation in patients receiving immunosuppression with organ transplants or treatment with any of the many immunosuppressive agents in use today for the treatment of multiple different diseases, or in patients receiving the direct-acting antivirals used in the treatment of hepatitis C virus (HCV). This article covers the immunology of HBV reactivation, mechanisms of viral clearance, and recommendations for screening and prophylaxis.

Organ transplantation is a lifesaving procedure for many patients. To prevent rejection or graft-versus-host disease, recipients require long-term immunosuppression. In patients who have ever been exposed to hepatitis B, it is possible for reactivation to occur; this includes patients who are anti-hepatitis B core antibody-positive only or both anti-hepatitis B core antibody-positive and hepatitis B surface antibody-positive. The susceptibility to this varies with the nature of the transplant. Hepatitis B can be transmitted from donor to recipient. It is important to assess the hepatitis B status and formulate a strategy to prevent transmission and prevent reactivation.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Background Recent single-center studies promote oral penicillin challenges, without skin testing, in patients with low risk/likelihood of true allergy. However, how best to define a low-risk penicillin allergy history is uncertain. Objective To statistically determine an optimal low-risk definition, to select patients for safe outpatient penicillin challenges, without skin testing. Methods In a multicenter Australian study (February 2016 to May 2018), testing strategy (skin test and/or oral penicillin challenge) and outcomes were retrospectively collected for all penicillin-allergic patients. Statistical modeling was performed with 8 low-risk definitions, to determine an optimal low-risk definition. Results A total of 447 subjects (mean age, 45.3 years; 63.8% females) were analyzed. A history of benign, immediate, or delayed rash, more than 1 year before review, was the optimal low-risk definition. A total of 244 of 447 (54.6%) patients met this definition, of which 97.1% tolerated a 1- or 2-dose penicillin challenge, with no anaphylaxis in those who reacted. Of 203 patients designated higher risk, 54 (26.6%) had their allergy confirmed by skin test (n = 45) or challenge (n = 9). Conclusions History of penicillin-associated rash (without angioedema, mucosal ulceration, or systemic involvement), more than 1 year ago, is sufficient to select a patient for a direct oral penicillin challenge. This large multicenter study demonstrates that this approach appears safe, and risk is comparable to that in other procedures being performed in primary care in Australia. The higher risk patients are more likely to benefit from skin testing. This simple risk-based delabeling strategy could potentially be used by nonallergists, leading to more efficient penicillin allergy delabeling service provision.

BACKGROUND: Antibiotic allergies are frequently reported and have significant impacts upon appropriate prescribing and clinical outcomes. We surveyed infectious diseases physicians, allergists, clinical immunologists and hospital pharmacists to evaluate antibiotic allergy knowledge and service delivery in Australia and New Zealand. METHODS: An online multi-choice questionnaire was developed and endorsed by representatives of the Australasian Society of Clinical Immunology and Allergy (ASCIA), Australasian Society of Infectious Diseases (ASID) and Society of Hospital Pharmacists Australia (SHPA). The 37-item survey was distributed in April 2015 to members of ASCIA, ASID, SHPA and Royal Australasian College of Physicians. RESULTS: Of 277 respondents, 94% currently use or would utilise antibiotic allergy testing (AAT) and reported seeing up to 10 patients/week labelled as antibiotic-allergic. Forty-two per cent were not aware of or did not have AAT available. Most felt that AAT would aid antibiotic selection, antibiotic appropriateness and antimicrobial stewardship (79%, 69% and 61%, respectively). Patients with histories of immediate hypersensitivity were more likely to be referred than those with delayed hypersensitivities (76% vs. 41%, p=0.0001). Lack of specialist physicians (20%) and personal experience (17%) were barriers to service delivery. A multidisciplinary approach was the preferred AAT model (53%). Knowledge gaps were identified, with the majority over-estimating rates of penicillin/cephalosporin (78%), penicillin/carbapenem (57%) and penicillin/monobactam (39%) cross-reactivity. CONCLUSIONS: A high burden of antibiotic allergy labelling and demand for AAT is complicated by a relative lack availability or awareness of AAT services in Australia and New Zealand. Antibiotic allergy education and deployment of AAT, accessible to community and hospital-based clinicians, may improve clinical decisions and reduce antibiotic allergy impacts. A collaborative approach involving ID physicians, pharmacists and allergists/immunologists is required.

Summary The aim of this study was to determine the prevalence and type of autoantibodies in a general Australian population cohort. Samples collected from 198 individuals included in a cross sectional Busselton Health Study were tested using autoantibody assays routinely performed at Clinical Immunology, PathWest Laboratory Medicine, Western Australia. At least one autoantibody was detected in 51.5% of individuals (males = 45.1%, females = 58.3%). The most frequently detected serum autoantibodies were anti-beta-2-glycoprotein I (12.1%) followed by anti-smooth muscle (11.6%) and anti-thyroid peroxidase (8.6%). Vasculitis associated anti-neutrophil cytoplasmic antibodies were present in 5.1%, while anti-nuclear antibodies were detected in 8.6% of individuals. Notably, 65% of positive results were detected at low levels with the exception of anti-myeloperoxidase and anti-beta 2 glycoprotein I IgG antibodies. Autoantibodies are commonly detected at low levels in a predominantly Australian or European population cohort. No large Australian study has yet provided these data for contemporary routine tests. This paper gives important information on the background frequency of autoantibodies in the general population. Due to the nature of this study we are unaware of whether these individuals have subsequently developed an autoimmune disease, however this was not clinically diagnosed at the time of sample collection.

Background and aim Pediatric patients increasingly report allergies, including allergies to food and medications. We sought to determine the incidence and, nature of parent‐reported allergies in children presenting for surgery and its significance for anesthetists. Methods We prospectively collected data on admissions through our surgical admission unit over a 2‐month period at a pediatric tertiary care teaching hospital. Data collected included patient demographics, history of atopy, with more comprehensive information collected if an allergy was reported. A clinical immunologist and an anesthetist reviewed the documentation of all patients reporting an allergy. Results We reviewed 1001 pediatric patients, 158 (15.8%) patients with parent‐reported allergies; to medications/drugs (n = 73), food (n = 66), environmental allergens (dust/grasses, n = 35), tapes/dressings (n = 27), latex (n = 4), and venom (eg, bee, wasp, n = 9). Forty‐one patients reported antibiotic allergies, with Beta‐lactam antibiotics being the most common, with the majority presenting with rash alone (57%). Ten patients reported allergies to nonsteroidal anti‐inflammatory drugs and eight to opioids. Twenty‐four patients reported egg and/or peanut allergy. Only 3/1001 (0.3%) patients were deemed to have evidence of likely IgE‐mediated drug allergy. Of the reported allergies, only 60 (38.2%) had been investigated prior, most likely to be followed up were food (53%) and environmental allergies (44.4%). Only 4/73 (5.5%) reported medication allergies had further follow‐up. Just four patients (0.4% of the entire cohort) had drug sensitivities/allergies that were likely to majorly alter anesthesia practice. Conclusion Only the minority of parent‐reported allergies in pediatric surgical patients were specialist confirmed and likely to be clinically relevant. Self‐reported food allergy is commonly specialist verified whereas reactions to medications were generally not. Over‐reporting of allergies is increasingly common and limits clinician choice of medications. Better education of patients and their families and more timely verification or dismissal of parent‐reported reactions is urgently needed.

Objective To evaluate the prevalence of anti-AQP4 antibody in serum and CSF samples from patients being investigated for possible neuromyelitis optica spectrum disorder (NMOSD) referred to the PathWest State reference laboratory using a sensitive cell-based assay (CBA). Background NMOSD is an inflammatory CNS disease distinct from MS, which is relatively rare in Western countries. A proportion of patients with NMOSD have detectable serum IgG antibodies that target the water channel aquaporin-4 (AQP4-IgG), but the frequency varies in different populations studied and according to the assay method employed. Methods Sera or CSF from a diagnostic cohort of 196 consecutive patients with possible NMOSD which had previously been screened by indirect immunofluorescence (IIF) on primate cerebellum were re-tested for AQP4-IgG reactivity to the M1 and M23 isoforms of AQP4 using a commercial CBA. A control group of 205 patients with definite MS was also included in the study. Results Of the 196 patients, only 5 sera were AQP4-IgG positive, representing 2.6% of patients in the diagnostic cohort. All 5 AQP4-IgG positive patients fulfilled the 2015 revised diagnostic criteria for NMOSD and were females of varied ethnic origins, 4 of whom had longitudinally extensive transverse myelitis. The CBA confirmed AQP4-IgG positivity in the four patients previously reported as positive by IIF, and an additional patient with NMOSD who had previously been diagnosed as MS was also identified. None of the 205 MS sera were AQP4-IgG positive. Conclusions Our study confirms the utility and greater reliability of the M1/M23 CBA for detecting AQP4-IgG in patients with possible NMOSD, and indicates a prevalence of seropositive NMOSD in the Western Australian population similar to that in other Western populations.

AIM To determine if skin testing (ST) in addition to extended oral provocation challenge (OPC) is necessary for beta-lactam allergy verification in an Australian paediatric population. METHODS This was a retrospective study (176 children) that undertook assessments for beta-lactam allergy from 2006 to 2015 at a tertiary paediatric hospital. Patients either underwent direct OPC without ST or ST plus challenge if ST was negative. RESULTS The analysis included children with a history of varying rash types/severity as well as angioedema and reported anaphylaxis. A direct OPC was undertaken in 73 children. Three children reacted with one anaphylaxis. A total of 103 children underwent ST, with 13 children (12.6%) reacting. Of the 90 who subsequently proceeded to OPC, 4 reacted. A total of 132 children were given an extended oral course of the culprit antibiotic, to which 6 children reacted. CONCLUSIONS A direct OPC with the culprit drug in Australian children can be safely performed, avoiding resource-intensive and painful ST. Our data demonstrate that a prior history of anaphylaxis does not necessarily predict IgE-mediated allergy, as detected by positive immediate ST or reactions to oral challenge. Such history should not detract from efforts to assess these children for antibiotic allergy. We suggest that extended courses of at least 5 days are important in paediatric antibiotic de-labelling as six children (4.5% of those who were prescribed the extended course) reacted in our study and even developed symptoms late in the extended course, from days 2 to 6.

Host hepatitis C virus (HCV)-specific T cell responses and the ability of the virus to escape this response are important correlates of infection outcome. Understanding this host-viral interplay has been difficult given the often asymptomatic nature of acute HCV infection. We studied a recent transmission case to determine whether adapted viral strains can be transmitted and influence the recipient's anti-HCV T cell response. The diversity of viral populations was examined using next-generation sequencing, and HCV-specific T cell interferon (IFN)-γ responses were assessed using a peptide panel representing the autologous viruses. HCV-specific T cell responses in the source were directed against peptides that did not match the dominant autologous virus but rather low-frequency variants, implying existing viral adaptation in the source strain. Most HCV T cell epitopes that elicited an IFN-γ response in the source did not in the recipient, despite the pair sharing human leukocyte antigen alleles that govern antigen presentation and similar autologous viruses. Intrahost HCV variation in the recipient fell within predicted T cell epitopes, suggesting alternative targets of the immune response. These data suggest that transmission of adapted viral species can direct the host's HCV-specific immune response profile during acute infection.