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Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda.Copyright © 2021 Royal Australasian College of Physicians.

Objectives: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD). Method(s): All rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance. Result(s): The mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22-4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19-5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78-4.05; p < .001]) and number of COVID-Safe measures practiced (OR: 1.54 [95% CI: 1.05-2.26; p = .027]). Vaccine acceptance correlated with positive beliefs regarding vaccine efficacy (r = 0.40; p < .001) and safety (r = 0.36; p < .001). Vaccine acceptance correlated negatively with concerns regarding side-effects (r = -0.30; p < .001) and vaccine-associated RMD flare (r = -0.21; p < .001). In vaccine-hesitant respondents, 39.2% were more likely to accept vaccination if given a choice of which vaccine they receive and 54.5% if their rheumatologist recommended it. Twenty-seven percent of patients on immunomodulators were willing to withhold medications while 42.1% were willing if advised by their rheumatologist. Conclusion(s): SARS-COV-2 vaccine hesitancy is prevalent amongst RMD patients and associated with concerns regarding vaccine safety, efficacy, side effects and RMD flare. Clinician recommendation, vaccine choice and communications targeting patient concerns could facilitate vaccine acceptance. Significance and Innovations Vaccine hesitancy is prevalent in RMD patients Vaccine acceptance is associated with beliefs regarding vacc

Background: Prophylactic immunoglobulin (Ig) replacement and prophylactic oral antibiotics (PA) are used to prevent infections in patients with haematological malignancies and acquired hypogammaglobulinemia. Ig has been shown to reduce infection risk, but is costly and in limited supply. PA have been shown to reduce infection risk in other patient populations and are less expensive, but have side-effects and can increase antimicrobial resistance rates. Guidelines and clinical practice vary internationally, with some recommending a trial of PA prior to commencing Ig replacement, and others omitting PA. The efficacy, safety and cost-effectiveness of Ig and PA have not been directly compared in a randomised controlled trial (RCT) in patients with acquired hypogammaglobulinemia secondary to haematological malignancies. Aim(s): To determine the feasibility of delivering PA as an alternative to Ig replacement in patients with haematological malignancies and acquired hypogammaglobulinemia. Method(s): Phase II, multicentre, feasibility RCT (ACTRN12616001723471). Eligible patients had acquired hypogammaglobulinemia due to a haematological malignancy, a history of recurrent or severe bacterial infections or an IgG level <4g/L (excluding paraprotein), and had a life expectancy more than 12 months. Exclusion criteria included prior allogeneic haematopoietic stem cell transplant and prior Ig replacement in the preceding 3 months. Patients were randomised to receive Ig (0.4g/kg IV every 4 weeks, modified to achieve an IgG trough level >= lower limit of reference range; or 0.1g/kg/week SC, modified to achieve an IgG trough level of >= lower limit of reference rage) or daily oral prophylactic antibiotics (trimethoprim-sulfamethoxazole 160mg/800mg, with 100mg doxycycline as an alternative for hypersensitivity) for 12 months at a 1:2 ratio. Randomisation was stratified by site. Patients allocated to PA were allowed to cross over to Ig if they experienced a CTCAE >= Grade 3 infection.

Aims: To assess the COVID-19 vaccine understanding, attitudes and hesitancy in renal transplant recipients prior to vaccination. Background(s): Transplant recipients are particularly vulnerable to the consequences of COVID-19 infection. COVID-19 vaccine hesitancy is currently a major public health concern. Method(s): An anonymous 'COVID-19 vaccine understanding, and attitudes' online survey was distributed to kidney transplant recipients at our centre. Participants were categorised by intention to have the vaccine: yes, no and undecided. Comparisons were made between the yes and undecided (hesitant) groups. Result(s): Of 876 surveys sent, 473 recipients responded (response rate 54%). 346 (73.15%), and 105 (22.20%) recipients were in the yes and undecided categories respectively (no group 22 (4.65%) are not considered further). Yes and undecided groups were similarly concerned about their risk of COVID-19 infection. Relative to the yes group, the undecided group were younger (mean age 58.53, SD 12.09 vs.54.69, SD 12.49, p = 0.005), but were not different in other characteristics including gender, education level, occupation status, transplant duration or comorbidities (p-value>0.05 for all). The undecided group felt less positive about the vaccine, less relief it was available and had greater concerns about vaccine safety, effectiveness, and potential side effects (p-values all <0.001). The undecided group also felt more need for vaccine specific information and a recommendation from their nephrologist before committing to vaccination (p < 0.001). Recipients ranked mask wearing, handwashing, and social distancing (both individually and collectively) more effective in reducing COVID-19 infection risk than vaccination (p < 0.001). Conclusion(s): Vaccine hesitant recipients had concerns pertaining to vaccine safety and effectiveness. Vaccine specific information and a recommendation from their Nephrologist were identified as mechanisms to increase vaccine acceptance in

Background: Fungal peritonitis is associated with significant morbidity and mortality and commonly leads to peritoneal dialysis (PD) technique failure. Candida albicans and Candida parapsilosis are the most common fungal organisms causing PD peritonitis. Clinical experience with rare candida species is important to inform practice because with clinical data lacking, recommendations are largely based on laboratory data. We present a case of Candida guilliermondii PD peritonitis. Case Report: A 70-year old male was admitted for an elective arteriovenous fistula ligation. During his admission he developed a cloudy dialysate but remained clinically well with no fevers, abdominal pain or systemic symptoms. His peritoneal fluid microscopy revealed a white cell count of 1410 x 106/L, the gram stain showed no growth, and his culture isolated Candida guilliermondii. The fluconazole, voriconazole, amphotericin B and caspofungin minimum inhibitory concentrations (MIC) were 4 mg/L, 0.06 mg/L, 0.25 mg/L, and 0.5 mg/L respectively. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints data suggests fluconazole resistance with MIC > 4 mg/L for C. albicans and C. parapsilosis. The susceptibility data for C. guilliermondii is not yet clearly established. The patient underwent a removal of his Tenkhoff catheter and was successfully treated with a two-week course of oral fluconazole 200 mg daily despite the potentially reduced in vitro susceptibility, as inferred from other common candida species' resistance patterns. Conclusion(s): C. guilliermondii PD peritonitis is rare. It is reportedly a more resistant candida species with a diminished susceptibility to fluconazole and echinocandins. Lack of clinical experience may make interpreting susceptibility data of rare fungal pathogens unreliable. Although in vitro results suggested potentially reduced fungal susceptibility, our case demonstrates that clinical cure is achievable with short course fluconazole

Objective: To identify barriers and enablers to COVID-19 vaccination in renal transplant recipients who are undecided about vaccination. Method(s): An online survey was distributed to 876 adult kidney transplant recipients at a tertiary referral service, who had not been vaccinated against COVID-19. The survey assessed willingness to be vaccinated, attitudes toward COVID-19 vaccines, and barriers and enablers to proceeding with vaccination. Result(s): The survey response rate was 54% (473/876). Three hundred and forty-six (73.1%) participants planned to receive vaccination (yes group), 105 (22.2%) were undecided, and 22 (4.7%) refused vaccination. The undecided group were younger but were not different in other demographic characteristics to the yes group. The undecided group were less positive toward (34.29% vs. 91.3%, p <.001) and more concerned about (93.3% vs. 25.1%, p <.001) vaccination than the yes group. Their concerns related to vaccine safety (including harm to their transplant), poor efficacy, and a lack of rigorous testing in transplant recipients. Undecided recipients had received less vaccine-specific information from medical specialists than the yes group. Most undecided participants (95.1%) were willing to proceed with vaccination with appropriate supports. The most desired supports were information and a recommendation to proceed with vaccination from their treating transplant specialist and team. Conclusion(s): Concerns about vaccine safety (including harm to transplant), poor vaccine efficacy, and lack of rigorous testing were barriers to vaccine uptake. Most undecided recipients would proceed with vaccination with specific recommendations and vaccine information provided by their transplant specialist/team. These simple interventions can be readily implemented to optimize vaccine uptake.Copyright © 2021 Wiley Periodicals LLC

Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda.

INTRODUCTION: The impact of medical student psychological distress on academic performance has not been systematically examined. This study provided an opportunity to closely examine the potential impacts of workplace and study related stress factors on student's psychological distress and their academic performance during their first clinical year. METHOD(S): This one-year prospective cohort study was performed at a tertiary hospital based medical school in Melbourne, Australia. Students completed a questionnaire at three time points during the year. The questionnaire included the validated Kessler psychological distress scale (K10) and the General Health Questionnaire-28 (GHQ-28), as well as items about sources of workplace stress. Academic outcome scores were aggregated and correlated with questionnaire results. RESULT(S): One hundred and twenty six students participated; 126 (94.7%), 102 (76.7%), and 99 (74.4%) at time points one, two, and three, respectively. 33.1% reported psychological distress at time point one, increasing to 47.4% at time point three. There was no correlation between the K10 scores and academic performance. There was weak negative correlation between the GHQ-28 at time point three and academic performance. Keeping up to date with knowledge, need to do well and fear of negative feedback were the most common workplace stress factors. CONCLUSION(S): Poor correlation was noted between psychological distress and academic performance.

Introduction Multimodal interventions (MMI) are frequently used in various healthcare settings to encourage change in healthcare personnel practices and improve patient safety. In 2013, an MMI conducted in an Australian metropolitan ED used clinician champions, guidelines, education sessions and promotional materials to encourage a reduction in unused and inappropriate peripheral intravenous cannulas (PIVC). A 60-day postintervention demonstrated a successful reduction in the number of unused PIVCs without changes in appropriate insertions. We aimed to investigate if this MMI produced a sustained effect in reducing the frequency of unused PIVCs inserted in this ED. Methods A single-centre retrospective cohort study of adult patients presenting to the above ED in Victoria, Australia, was conducted in April 2018. A random sample of 380 patients with a PIVC inserted in ED was assessed to determine if the PIVC was used (termed Long-term follow-up'). The appropriateness of unused PIVCs was assessed. Our findings were compared with previously collected data in 2013 ( Pre-Intervention' and Immediately Post-Intervention') to determine a sustained reduction in the frequency of unused PIVC insertions was achieved. Long-term analysis of the MMI, including the overall frequency of PIVC insertions in ED before and after the MMI, was also collected. Results In our Long-term follow-up cohort, 101 of 373 (27.1%, 95% CI 22.6% to 31.9%) PIVCs were unused (seven cases excluded). This was significantly lower than the Pre-Intervention cohort (139/376, 37.0%, 95% CI 32.1% to 42.1%). While not significant, the frequency of unused PIVCs in the Post-Intervention cohort was lower in comparison (73/378, 19.3%, 95% CI 15.4% to 23.7%). No significant change in the appropriateness of unused PIVCs was observed between the Post-Intervention and Long-term follow-up. The overall proportion of patients receiving a PIVC has remained low since the MMI. Conclusion An MMI aimed at reducing unused PIVC in

Aim: To investigate the incidence of severe infections (SI) in RA patients, identify associated risk factors, and propose a simple infection risk screening tool. Method(s): Between January and July 2019, consenting patients with a diagnosis of RA were recruited consecutively from an Australian tertiary hospital's RA clinic. The primary outcome was a severe infection (any infection requiring hospital admission) between January 2018 and July 2019. We collected data from patients, medical records, and pathology tests. We used validated scores such as the disease activity score of 28 joints (DAS-28) and the Charlson comorbidity index to assess disease activity and comorbidity burden. Multivariable logistic regression was used for statistical analysis. Result(s): We recruited 263 eligible patients. 40% were on biologic therapies. Forty-five confirmed SI episodes occurred in 34 patients (13%), corresponding to 10.8 SIs per 100-patient-years. Respiratory (53%) and urinary tract infections (13%) were the most common. Glucocorticoid-use was lower in this cohort (29%) and not significantly associated with SI. Biologics were not significantly associated with SI. On multivariable analysis, the most significant risk factors included low total lymphocytes (odds ratio (OR) 4.08), a previous infection within the last three years (OR 3.58), a Charlson Comorbidity Index of two or more (OR 2.69), and higher disease activity (OR 1.35 per 0.5-increase in DAS-28). The model incorporating these factors had an area under ROC curve of 0.82. Conclusion(s): This was one of the first Australian studies to evaluate severe infection rates in a real-world RA cohort. SI rates were high. Lymphopenia, disease activity, comorbidity burden, and previous SI were independent risk factors for infection. Our model is a composite of easily assessable clinical and biological parameters, with excellent predictive potential for SI risk. It may be developed into a tool for rapid screening of high-risk patients

Multiplex polymerase chain reaction (PCR) testing has revolutionised microbiological practice but also increased the number of positive results of uncertain significance. This phenomenon has been seen in the increasing detection of cytomegalovirus (CMV) in mucocutaneous swabs for herpesviruses, the microbiological significance of which is a priori unclear. The aim of our study was to determine if an incidental finding of a positive CMV result represented CMV disease, if it facilitated a timely diagnosis of CMV disease or whether there were any deleterious outcomes. We performed a retrospective review of patients with an incidentally positive PCR result for CMV on external and mucosal swabs, including medical comorbidities and presence of immunosuppression, subsequent investigations, whether a diagnosis of CMV disease was made, and treatment. CMV detection was infrequent, detected in 158 (3.4%) of 4626 herpes multiplex PCR tests performed. The majority (60.4%) of patients were immunocompromised, and amongst these patients a positive swab represented a new diagnosis or already known CMV disease in 14%. In seven patients (5%), all of whom were immunocompromised, the positive CMV PCR on a swab led to further investigation and subsequent diagnosis and treatment of CMV disease. Whilst not recommended for diagnosis of CMV disease, if CMV is detected on a mucocutaneous swab in an immunocompromised patient, further assessment and investigation for CMV disease should be undertaken.Copyright © 2020 Royal College of Pathologists of Australasia

Background: Individuals splenectomised for trauma have lower infection rates than those splenectomised for other conditions. Residual functional splenic tissue (FST) after splenectomy may provide ongoing immunological protection. Aim(s): To quantify the prevalence and volume of residual FST post-splenectomy using standard testing. Method(s): Splenectomised adults were recruited from the Spleen Australia clinical registry. Eligible individuals had been splenectomised at least 1 year prior to their visit and resided in Victoria. Splenic function was identified by evaluating Howell-Jolly bodies and IgM memory B cells. A 99m-Technetium-labelled, heat-denatured erythrocyte scintigraphic scan was performed if splenic function was detected. Result(s): Initially, 75 splenectomised individuals (all cause) were recruited, with a median of 58 years of age and who were splenectomised a median of 14 years previously. The most common indications for splenectomy were trauma (30.7%) and haematological disease (28.0%). Scintigraphy identified FST in nine individuals (12.0%). Eight had been splenectomised for trauma. In this cohort, 34.8% of individuals splenectomised for trauma had residual FST. To explore our findings further, 45 additional individuals were recruited, predominately individuals splenectomised for trauma. Twenty-five individuals completed assessments by December 2018. An additional 11 individuals had FST, of whom 9 had been splenectomised for trauma. Overall, we identified 20 individuals with residual FST. Volumes ranged from 2.2 to 216.0 cc. We saw individuals with accessory spleens and splenotic nodules and an individual with both. Seventeen individuals had been splenectomised for trauma. Conclusion(s): Residual FST is commonly seen in individuals splenectomised for trauma. It can present in varying distributions and of varying volume. The clinical significance is unclear.Copyright © 2019 Royal Australasian College of Physicians

Legionella pneumophila is a well-known cause of pneumonia that is infrequently cultured in clinical practice. We report a case of an immunocompromised patient with persistently positive L. pneumophila cultures from invasive respiratory samples despite prolonged treatment with appropriate antibiotics. In vitro testing showed that the isolate remained susceptible to ciprofloxacin and azithromycin.

Despite improvements in graft survival, solid organ transplantation is still associated with considerable infection induced morbidity and mortality. If we were able to show that serious infection risk was associated with excessive suppression of immune capacity, we would be justified in "personalizing" the extent of immunosuppression by carefully monitored reduction to see if we can improve immune compromize without increasing the risk of rejection. Reliable biomarkers are needed to identify this patients at an increased risk of infection. This review focuses on the currently available evidence in solid organ transplant recipients for immune non-pathogen specific biomarkers to predict severe infections with the susceptibility to particular pathogens according to the component of the immune system that is suppressed. This review is categorized into immune biomarkers representative of the humoral, cellular, phagocytic, natural killer cell and complement system. Biomarkers humoral and cellular systems of the that have demonstrated an association with infections include immunoglobulins, lymphocyte number, lymphocyte subsets, intracellular concentrations of adenosine triphosphate in stimulated CD4+ cells and soluble CD30. Biomarkers of the innate immune system that have demonstrated an association with infections include natural killer cell numbers, complement and mannose binding lectin. Emerging evidence shows that quantification of viral nucleic acid (such as Epstein Barr Virus) can act as a biomarker to predict all-cause infections. Studies that show the most promise are those in which several immune biomarkers are assessed in combination. Ongoing research is required to validate non-pathogen specific immune biomarkers in multi-centre studies using standardized study designs.Copyright © 2018 Elsevier Inc.

Purpose: The aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. Methods and Materials: A prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. Result(s): After 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P =.001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P =.060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. Conclusion(s): Monitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.Copyright © 2018 Elsevier Inc.

Objective: Our objective was to examine the impact of a human factor-designed multimodal intervention on the proportion of unused peripheral i.v. cannula (PIVC) insertion in our ED. Method(s): A pre- and post-multimodal intervention retrospective cohort study was conducted using a structured electronic medical record review within a single adult tertiary ED in Australia. Pre-intervention data was collected 30 days prior to the multimodal intervention, with 30 day post-intervention data collected 3 months after the intervention commenced. The rates of PIVC inserted, the unused rate and the unused but appropriately inserted cannulas were the main outcome measures. Result(s): Intravenous cannula insertion rates decreased by 12.9% (95% confidence interval [CI] 12.19-13.61) between the pre-intervention (1413/4167 [33.9%]; 95% CI 32.5-35.4) and post-intervention cohort (928/4421 [21.0%]; 95% CI 19.8-22.2). An analysis of 754 cases (376 pre-intervention and 378 post-intervention) showed that 139 of 376 (37.0%; 95% CI 32.1-42.1) i.v. cannulas were unused pre-intervention, while 73 of 378 (19.3%; 95% CI 15.4-23.7) was unused post-intervention; an absolute reduction of 17.7% (95% CI 14.98-20.42). The relative risk of an unused i.v. cannula was 0.52 (95% CI 0.41-0.67). The proportion of unused but appropriately inserted i.v. cannulas remained unchanged in both cohorts, with a relative risk of 0.91 (95% CI 0.58-1.42). Conclusion(s): Our multimodal intervention successfully reduced the number of unused PIVCs inserted in the ED, with a reduction in overall and unused PIVC insertions without any change in appropriate insertions.Copyright © 2018 Australasian College for Emergency Medicine and Australasian Society for Emergency Medicine

Background: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. Method(s): We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. Result(s): Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). Conclusion(s): Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.Copyright © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Cytomegalovirus (CMV) infection represents a major cause of morbidity and mortality in immunocompromised hosts. Skin ulceration is a rare manifestation of tissue-invasive disease, with the anogenital region being the most typical site of involvement. We present a case of CMV ulceration on the right leg occurring 16 years following renal transplantation and 1 year after adjuvant radiotherapy for a Marjolin ulcer at this site. We suggest radiotherapy may provide a mechanism for local reactivation of the virus in the skin of seropositive patients.Copyright © 2018 The Australasian College of Dermatologists

Objective: To evaluate quality of patient knowledge and rates of adherence to guidelines amongst splenectomised patients registered to the Spleen Australia registry. Method(s): Registrants recruited for assessment of residual splenic function post-splenectomy also underwent an assessment of quality of knowledge and a review of their long-term management. Eligible patients were >= 18 years of age, registered to the Spleen Australia clinical registry and had been splenectomised at least 1 year prior to their visit. Quality of knowledge was assessed using a validated questionnaire used in similar studies. Receipt of immunisations was validated by record review. Chemoprophylaxis use was self-reported by patients. Adherence was evaluated using Australian guidelines. Result(s): 77 patients were evaluated for education and adherence. 58% were female, mean age was 58 years, and median duration since splenectomy was 14 years. Most common indications for splenectomy were trauma and haematological conditions. 77% had good knowledge of key educational points to reduce chances of infection. Adherence to immunisations varied with poor adherence to vaccines introduced after 2010. Only 6 patients were adherent to all recommended immunisations. Increasing duration since registration was associated with poorer 13vPCV (p = 0.008) and 4vMenCV adherence (p = 0.001). Over 70% either currently or had previously used daily chemoprophylaxis and 66% had a supply of emergency antibiotics. Conclusion(s): Although registrants are receiving initial and booster vaccinations, they do not receive newly recommended vaccines. In order to maintain long-term adherence, we recommend streamlining health information systems, improving awareness strategies and improving financial access to vaccinations in the community with additional awareness of the activities of the registry.Copyright © 2018, © 2018 Taylor & Francis Group, LLC.

The aim of this study was to determine if natural killer cell number (CD3-/CD16+/-/CD56+/-) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P =.018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P <.0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P =.051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.Copyright © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons

The aim of this study was to determine if natural killer cell number (CD3- /CD16± /CD56± ) and cytotoxic killing function predicts severity and frequency of infection in kidney transplant recipients. A cohort of 168 kidney transplant recipients with stable graft function underwent assessment of natural killer cell number and functional killing capacity immediately prior to entry into this prospective study. Participants were followed for 2 years for development of severe infection, defined as hospitalization for infection. Area under receiver operating characteristic (AUROC) curves were used to evaluate the accuracy of natural killer cell number and function for predicting severe infection. Adjusted odds ratios were determined by logistic regression. Fifty-nine kidney transplant recipients (35%) developed severe infection and 7 (4%) died. Natural killer cell function was a better predictor of severe infection than natural killer cell number: AUROC 0.84 and 0.75, respectively (P = .018). Logistic regression demonstrated that after adjustment for age, transplant function, transplant duration, mycophenolate use, and increasing natural killer function (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74-0.90; P < .0001) but not natural killer number (OR 0.96, 95% CI 0.93-1.00; P = .051) remained significantly associated with a reduced likelihood of severe infection. Natural killer cell function predicts severe infection in kidney transplant recipients.

BACKGROUND: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. METHODS: We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. RESULTS: Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). CONCLUSION: Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.

To identify risk factors for infection in patients with diffuse large B cell lymphoma (DLBCL) undergoing rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone (R-CHOP) treatment. All patients with DLBCL who received R-CHOP from 2004-2014 in a tertiary Australian hospital were identified and information collected from hospital admission data, laboratory results and medical record review. Infection was defined as hospitalisation with an ICD-10-AM diagnostic code for infection. Risk factors for infection and association between infection and survival were modelled using Cox proportional hazards regression. Over the 10-year period there were 325 patients; 191 (58.8%) males, median age 66 years. 206 (63.4%) patients experienced >=1 infection. Independent predictors of infection were Charlson comorbidity index score (hazard ratio [HR] 3.60, p=0.002), Eastern Cooperative Oncology Group (ECOG) performance status (HR 2.09 p=<0.001) and neutropenia (HR 2.46, p=<0.001). 99 (31%) patients died. Infection was an independent predictor of survival (HR 3.27, p=<0.001, as were age (HR 2.49, p=0.001), Charlson comorbidity index (HR 4.34, p=<0.001), ECOG performance status (HR 4.33, p=0.045) and neutropenia (HR 1.95, p=0.047). Infections are common and infection itself is an independent predictor of survival. Patients at highest risk of infection and death are those with multiple comorbidities, poor performance status and neutropenia.

Aim The mechanisms underlying increased thrombogenicity in splenectomy are poorly understood. We assessed a potential role for platelets by analysing surface expression of key platelet-specific receptors glycoprotein (GP)Iba, GPVI and aIIbb3, and a platelet activation marker, P-selectin. GPIba, that binds von Willebrand factor and other ligands, is constitutively shed from aging platelets, and its surface density is crucial for both thrombus formation and platelet clearance through interactions with phagocytic cells. GPIba also forms a non-covalent complex with GPVI, which binds collagen and fibrin. GPIba/GPVI initiate platelet adhesion, leading to platelet activation and aggregation, secretion of procoagulant factors and thrombus formation. Methods Whole blood from same-day healthy controls (n=15) or splenectomy (n=30) was centrifuged to obtain platelet-rich-plasma, and stained with phycoerythrin (PE)-labelled antibodies against GPIba (PE-AK2), GPVI (PE-1G5), aIIb (PE-CD41a), CD9 (PE-CD9), and P-selectin (PE-CD62P) using standardized protocols, and analysed using a FACSCalibur. Results Preliminary analysis suggested that compared to healthy controls, platelets from splenectomy cases showed significantly decreased surface expression of GPIba (p <0.0001) and GPVI (p=0.0035). In contrast, there was no significant difference in relative surface expression of aIIbb3 (p=0.759) and CD9 (p=0.112). Further, consistent with increased platelet activation/secretion, expression of surface P-selectin was more variable and significantly elevated in splenectomy cf . control platelets (p=0.0005). ELISA analysis of stored plasma will be used to confirm whether decreased platelet GPVI is likely due to increased shedding, resulting in increased plasma sGPVI. Conclusion The results of this pilot study support a role for hyperactivated platelets post-splenectomy, and identify platelet-specific markers related to these changes. Methods and results developed here will enable future larger

Objectives: Asplenia and hyposplenism carry a significant risk of ongoing morbidity and mortality which can be reduced by education, vaccination and antibiotic use. We aimed to assess education and other methods of prevention in a cohort of patients with haemoglobinopathy in a tertiary referral centre, which also had access to a post-splenectomy registry created to reduce post-splenectomy infection risk. Method(s): A standardized questionnaire was used on patients who attended the service for regular therapy. Patients were also asked about standard post-splenectomy preventive therapies including antibiotics and vaccinations. Result(s): There were 49 patients who had either had a splenectomy or knew their spleen to be non-functional. Of these, nearly half knew themselves to be on the Victorian Spleen Registry (51.0%). The median knowledge score was 12 (range 4-17) out of a possible 18. Most significantly the benefits of the registry were not seen in terms of knowledge but in delivery of recommended vaccines and the use of a medical alert card. Conclusion(s): This study examined knowledge and attitudes about splenectomy in a cohort of haemoglobinopathy patients in an Australian tertiary referral centre. The majority had good or fair knowledge with a strong association of some elements of post-splenectomy care with being placed on a spleen registry and having received targeted education. Implementation of systematic approaches by medical staff is likely to be the main benefit of a clinical registry approach in this setting.Copyright © 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Microsporidia are intracellular organisms most commonly known to cause opportunistic infection in patients with human immunodeficiency virus (HIV). There have been several case reports of infection in solid organ and bone marrow transplant recipients. Here, we report a case of a non-HIV-infected renal transplant patient with microsporidiosis of the renal tract associated with acute graft dysfunction. We also review the literature of 12 previously reported cases of microsporidiosis in patients with renal transplants who had described graft involvement. We review the pattern of illness as well as the common renal biopsy features when microsporidial infection is associated with renal graft infection.Copyright © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

This narrative review summarizes the current literature relating to pneumococcal vaccination in adult solid organ transplant (SOT) recipients, who are at risk of invasive pneumococcal disease (IPD) with its attendant high morbidity and mortality. The effect of the pneumococcal polysaccharide vaccine has been examined in several small cohort studies in SOT recipients, most of which were kidney transplant recipients. The outcomes for these studies have been laboratory seroresponses or functional antibody titers. Overall, in most of these studies the transplant recipients were capable of generating measurable serological responses to pneumococcal vaccination but these responses were less than those of healthy controls. A mathematical model estimated the effectiveness of polysaccharide vaccination in SOT recipients to be one third less than those of patients with HIV. The evidence for the efficacy of the pneumococcal conjugate vaccine in SOT is based on a small number of randomized controlled trials in liver and kidney transplant recipients. These trials demonstrated that SOT recipients mounted a serological response following vaccination however there was no benefit to the use of prime boosting (conjugate vaccine followed by polysaccharide vaccine). Currently there are no randomized studies investigating the clinical protection rate against IPD after pneumococcal vaccination by either vaccine type or linked to vaccine titers or other responses against pneumococcus. Concerns that vaccination may increase the risk of adverse alloresponses such as rejection and generation of donor specific antibodies are not supported by studies examining this aspect of vaccine safety. Pneumococcal vaccination is a potentially important strategy to reduce IPD in SOT recipients and is associated with excellent safety. Current international recommendations are based on expert opinion from conflicting data, hence there is a clear need for further high-quality studies in this high-risk popula

Background: Clinical guidelines recommend vaccinations for solid-organ transplant recipients. However, concern exists that vaccination may stimulate adverse alloimmune responses. Method(s): We systematically reviewed the published literature regarding this aspect of vaccine safety. Electronic databases were searched for interventional and observational studies assessing de novo donor-specific antibodies (DSA) and rejection episodes after vaccination against infectious pathogens. Graft loss was also assessed. A meta-analysis was conducted for prospective, controlled studies. PRISMA reporting guidelines were followed. Result(s): Ninety studies (15,645 vaccinated patients and 42,924 control patients) were included. Twelve studies included control groups. The incidence of de novo DSA (14 studies) was 23 of 1,244 patients (1.85%) at 21 to 94 days. The incidence of rejection (83 studies) was 107 episodes in 5,116 patients (2.1%) at 0.7 to 6 months. Meta-analysis of prospective controlled studies (n = 8) showed no increased rejection risk with vaccination compared with no vaccination (RR 1.12, 95% CI 0.75 to 1.70). This finding was supported by data from 3 registry analyses. Conclusion(s): Although the current evidence lacks high-quality, controlled studies, the currently available data provide reassurance that clinicians should recommend appropriate vaccination for their transplant patients as the risk of de novo DSA and rejection is relatively low.Copyright © 2018 International Society for the Heart and Lung Transplantation

Background: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. Method(s): Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. Result(s): Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer >=1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. Conclusion(s): A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.Copyright © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

BACKGROUND: Conjugated pneumococcal vaccine is recommended for kidney transplant recipients, however, their immunogenicity and potential to trigger allograft rejection though generation of de novo anti-human leukocyte antigen antibodies has not been well studied. METHODS: Clinically stable kidney transplant recipients participated in a prospective cohort study and received a single dose of 13-valent conjugate pneumococcal vaccine. Anti-pneumococcal IgG was measured for the 13 vaccine serotypes pre and post vaccination and functional anti-pneumococcal IgG for 4 serotypes post vaccination. Anti-human leukocyte antigen antibodies antibodies were measured before and after vaccination. Kidney transplant recipients were followed clinically for 12 months for episodes of allograft rejection or invasive pneumococcal disease. RESULTS: Forty-five kidney transplant recipients participated. Median days between pre and post vaccination serology was 27 (range 21-59). Post vaccination, there was a median 1.1 to 1.7-fold increase in anti-pneumococcal IgG antibody concentrations for all 13 serotypes. Kidney transplant recipients displayed a functional antibody titer ≥1:8 for a median of 3 of the 4 serotypes. Post vaccination, there were no de novo anti-human leukocyte antigen antibodies, no episodes of biopsy proven rejection or invasive pneumococcal disease. CONCLUSION: A single dose of 13-valent conjugate pneumococcal vaccine elicits increased titers and breadth of functional anti-pneumococcal antibodies in kidney transplant recipients without stimulating rejection or donor-specific antibodies.

A cross-sectional survey of 265 adult patients with haematological malignancy, haemoglobinopathy or human immunodeficiency virus was performed to determine the potential risk of infection from animal exposures. One hundred and thirty-seven (52%) owned an animal; the majority were dogs (74%) and cats (39%), but 14% owned birds and 3% reptiles. Eighty percent engaged in behaviour with their animals that potentially put them at risk of zoonotic infections. The most frequent behaviours were picking up animal faeces 72 (52%), cleaning animal areas 69 (50%) and allowing animals to sleep in the same bed 51 (37%). Twenty-eight percent allowed the animal to lick their face. Of all patients, 80 (30%) had been bitten or scratched by an animal. Only 16% of those who owned pets could recall receiving education regarding safe behaviours around animals. These immunocompromised patients are at risk of infection through exposure to pets. Our study highlights the need for increased education of patients regarding how to remain safe around their pets.Copyright © 2017 Royal Australasian College of Physicians

To identify risk factors for infection in patients with diffuse large B cell lymphoma (DLBCL) undergoing rituximab, cyclophosphamide, vincristine, adriamycin and prednisolone (R-CHOP) treatment. All patients with DLBCL who received R-CHOP from 2004-2014 in a tertiary Australian hospital were identified and information collected from hospital admission data, laboratory results and medical record review. Infection was defined as hospitalisation with an ICD-10-AM diagnostic code for infection. Risk factors for infection and association between infection and survival were modelled using Cox proportional hazards regression. Over the 10-year period there were 325 patients; 191 (58.8%) males, median age 66 years. 206 (63.4%) patients experienced ≥1 infection. Independent predictors of infection were Charlson comorbidity index score (hazard ratio [HR] 3.60, p = 0.002), Eastern Cooperative Oncology Group (ECOG) performance status (HR 2.09 p = <0.001) and neutropenia (HR 2.46, p = <0.001). 99 (31%) patients died. Infection was an independent predictor of survival (HR 3.27, p = <0.001, as were age (HR 2.49, p = 0.001), Charlson comorbidity index (HR 4.34, p = <0.001), ECOG performance status (HR 4.33, p = 0.045) and neutropenia (HR 1.95, p = 0.047). Infections are common and infection itself is an independent predictor of survival. Patients at highest risk of infection and death are those with multiple comorbidities, poor performance status and neutropenia.

A cross-sectional survey of 265 adult patients with haematological malignancy, haemoglobinopathy or human immunodeficiency virus was performed to determine the potential risk of infection from animal exposures. One hundred and thirty-seven (52%) owned an animal; the majority were dogs (74%) and cats (39%), but 14% owned birds and 3% reptiles. Eighty percent engaged in behaviour with their animals that potentially put them at risk of zoonotic infections. The most frequent behaviours were picking up animal faeces 72 (52%), cleaning animal areas 69 (50%) and allowing animals to sleep in the same bed 51 (37%). Twenty-eight percent allowed the animal to lick their face. Of all patients, 80 (30%) had been bitten or scratched by an animal. Only 16% of those who owned pets could recall receiving education regarding safe behaviours around animals. These immunocompromised patients are at risk of infection through exposure to pets. Our study highlights the need for increased education of patients regarding how to remain safe around their pets.

Opportunistic infections have been reported infrequently in primary HIV infection. We report a case of cryptococcemia in primary HIV infection. To our knowledge there has not been such a case reported. Our case highlights the need for clinicians to be wary of other opportunistic infections, including cryptococcosis, in primary HIV infection.Copyright © 2016, © The Author(s) 2016.