ORCID Profile
0000-0003-0109-0725
Current Organisations
Royal Australasian College of Physicians
,
Monash University
,
University of Melbourne Melbourne Medical School
,
University of Melbourne
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Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15589
Abstract: Patients with haematological malignancies, haemopoietic stem cell transplant recipients and patients requiring admission to intensive care settings are at high risk for invasive candidiasis (IC). Over the past decade, there has been increased reporting of non‐ albicans species and fluconazole resistance in Australia. These guidelines provide updated evidence‐based recommendations for the diagnosis and management of IC in adult and paediatric haematology, oncology and intensive care settings. Optimal pharmacological and non‐pharmacological management are discussed. Recent studies strengthen the recommendation for an echinocandin agent as first‐line therapy for high‐risk patients with IC. Mortality benefit has also been demonstrated for non‐pharmacological management, including removal of central venous catheters, infectious diseases consultation and use of care bundles. Healthcare facilities managing immunocompromised patient populations should therefore adopt implementation strategies for these multimodal interventions.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12597
Abstract: Pathogenic yeast forms are commonly associated with invasive fungal disease in the immunocompromised host, including patients with haematological malignancies and patients of haemopoietic stem cell transplants. Yeasts include the Candida spp., Cryptococcus spp., Pneumocystis jirovecii and some lesser-known pathogens. Candida species remain the most common cause of invasive yeast infections (and the most common human pathogenic fungi). These guidelines present evidence-based recommendations for the antifungal management of established, invasive yeast infections in adult and paediatric patients in the haematology/oncology setting. Consideration is also given to the critically ill patient in intensive care units, including the neonatal intensive care unit. Evidence for 'pre-emptive' or 'diagnostic-driven antifungal therapy' is also discussed. For the purposes of this paper, invasive yeast diseases are categorised under the headings of invasive candidiasis, cryptococcosis and uncommon yeast infections. Specific recommendations for the management of Pneumocystis jirovecii are presented in an accompanying article (see consensus guidelines by Cooley et al. appearing elsewhere in this supplement).
Publisher: Springer Science and Business Media LLC
Date: 19-03-2016
Publisher: Massachusetts Medical Society
Date: 11-03-2021
Publisher: Springer Science and Business Media LLC
Date: 13-06-2011
DOI: 10.1038/BMT.2011.116
Publisher: Springer Science and Business Media LLC
Date: 21-06-2014
DOI: 10.1007/S11904-014-0213-0
Abstract: An immune reconstitution disorder occurs in up to 40 % of severely immunodeficient HIV patients who commence antiretroviral therapy (ART), with an immune reconstitution inflammatory syndrome (IRIS) being encountered most commonly. Differences in the immunopathogenesis of an IRIS associated with different types of pathogen have become apparent but common features have also been defined. These include severe immunodeficiency prior to commencing ART associated with a high pathogen load and 'compensatory' immune responses, particularly innate immune responses, which inadequately control the pathogen and increase the risk of immunopathology as the immune system recovers on ART. Prevention of an IRIS may be achieved by optimising therapy for opportunistic infections before ART is commenced, delaying ART or using immunomodulatory therapy to prevent or suppress the immune response that causes the immunopathology. However, further clinical studies are required to examine these options in a systematic manner for the various types of IRIS.
Publisher: Georg Thieme Verlag KG
Date: 23-09-2015
Abstract: Inhalation of Cryptococcus into the respiratory system is the main route of acquisition of human infection, yet pulmonary cryptococcosis goes mostly unrecognized by many clinicians. This delay in diagnosis, or misdiagnosis, of lung infections is due in part to frequently subtle clinical manifestations such as a subacute or chronic cough, a broad differential of diagnostic possibilities for associated pulmonary masses (cryptococcomas) and, on occasion, negative respiratory tract cultures. Hematogenous dissemination from the lung can result in protean manifestations, the most severe of which is meningoencephalitis. There are few clinical studies of pulmonary cryptococcosis and its pathogenesis is poorly understood. The main purpose of this review is to describe the epidemiology, clinical presentation, diagnosis, and treatment of pulmonary cryptococcosis to increase clinician's awareness of this diagnostic possibility and to enhance clinical management. Useful pointers to the approach and management of pulmonary cryptococcosis and the implications of disseminated disease are included, together with recommendations for future research.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15585
Abstract: This article introduces the fourth update of the Australian and New Zealand consensus guidelines for the management of invasive fungal disease and use of antifungal agents in the haematology/oncology setting. These guidelines are comprised of nine articles as presented in this special issue of the Internal Medicine Journal . This introductory chapter outlines the rationale for the current update and the steps taken to ensure implementability in local settings. Given that 7 years have passed since the previous iteration of these guidelines, pertinent contextual changes that impacted guideline content and recommendations are discussed, including the evolution of invasive fungal disease (IFD) definitions. We also outline our approach to guideline development, evidence grading, review and feedback. Highlights of the 2021 update are presented, including expanded scope to provide more detailed coverage of common and emerging fungi such as Aspergillus and Candida species, and emerging fungi, and a greater focus on the principles of antifungal stewardship. We also introduce an entirely new chapter dedicated to helping healthcare workers convey important concepts related to IFD, infection prevention and antifungal therapy, to patients.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15586
Abstract: Invasive fungal diseases (IFD) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFD is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug–drug interactions and the emergence of antifungal resistance. As the population at risk of IFD continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ antifungal stewardship (AFS) programmes and measures to monitor and prevent infection has become increasingly important. These guidelines outline the essential components, key interventions and metrics, which can help guide implementation of an AFS programme in order to optimise antifungal prescribing and IFD management. Specific recommendations are provided for quality processes for the prevention of IFD in the setting of outbreaks, during hospital building works, and in the context of Candida auris infection. Recommendations are detailed for the implementation of IFD surveillance to enhance detection of outbreaks, evaluate infection prevention and prophylaxis interventions and to allow benchmarking between hospitals. Areas in which information is still lacking and further research is required are also highlighted.
Publisher: Wiley
Date: 06-2008
DOI: 10.1111/J.1445-5994.2008.01727.X
Abstract: Hospital building works increase the risk of invasive fungal infections. Nosocomial outbreaks have been reported. A pre-emptive strategy for planned building works is paramount. The roles of HEPA filtration, air-s ling and modulation of 'routine' antifungal prophylaxis practice are discussed in the context of pre-emptive planning and outbreak management.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12593
Abstract: This article introduces the second revision of the Australian and New Zealand consensus guidelines for the use of antifungal agents in the haematology/oncology setting. The current update occurs within the context of a growing population at risk of invasive fungal disease, improved understanding of risk factors, availability of new diagnostic tests, a much-expanded evidence base and changing clinical paradigms. Here, we provide an overview of the history and purpose of the guidelines, including changes in scope since the last clinical update was published in 2008. The process for development, and for enabling review of draft recommendations by end-users and other relevant stakeholders, is described. The approach to assigning levels of evidence and grades of recommendation is also provided, along with a comparison to international grading systems.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2016
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-09-2018
Publisher: Springer New York
Date: 2014
Publisher: Elsevier BV
Date: 05-2022
Publisher: Informa UK Limited
Date: 03-07-2015
Publisher: Oxford University Press (OUP)
Date: 08-2013
Publisher: Wiley
Date: 18-07-2007
Publisher: Oxford University Press (OUP)
Date: 09-09-2020
Abstract: SARS-CoV-2 antibody testing allows quantitative determination of disease prevalence, which is especially important in high-risk communities. We performed anonymized convenience s ling of 200 currently asymptomatic residents of Chelsea, the epicenter of COVID-19 illness in Massachusetts, by BioMedomics SARS-CoV-2 combined IgM-IgG point-of-care lateral flow immunoassay. The seroprevalence was 31.5% (17.5% IgM+IgG+, 9.0% IgM+IgG−, and 5.0% IgM−IgG+). Of the 200 participants, 50.5% reported no symptoms in the preceding 4 weeks, of which 24.8% (25/101) were seropositive, and 60% of these were IgM+IgG−. These data are the highest seroprevalence rates observed to date and highlight the significant burden of asymptomatic infection.
Publisher: Oxford University Press (OUP)
Date: 02-2009
DOI: 10.1086/595894
Publisher: Oxford University Press (OUP)
Date: 07-05-2018
DOI: 10.1093/CID/CIY370
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-04-2019
Publisher: Springer London
Date: 2014
Publisher: Elsevier BV
Date: 05-2008
DOI: 10.1016/J.JHIN.2008.02.010
Abstract: We report the successful control of an outbreak of six cases of nosocomial invasive aspergillosis (IA) in our haematology unit coinciding with major hospital construction works. Infection control changes included unit relocation, impermeable barriers at construction site, face-masking and voriconazole prophylaxis of 18 further high-risk patients, none of which developed breakthrough IA. A multi-faceted pre-emptive approach involving clinicians, hospital management, engineering and building departments is essential in preventing nosocomial IA outbreaks.
Publisher: Mary Ann Liebert Inc
Date: 07-2018
Publisher: Oxford University Press (OUP)
Date: 07-2009
Publisher: American College of Physicians
Date: 02-2022
DOI: 10.7326/M21-3507
Publisher: Wiley
Date: 15-04-2009
Publisher: CSIRO Publishing
Date: 2011
DOI: 10.1071/SH10060
Abstract: Background The rise in serious complications of early syphilis, including neurosyphilis, particularly in those with HIV infection and in men who have sex with men (MSM), is of concern. Objectives: To review the manifestations and management of neurosyphilis in a population of HIV-infected MSM. Methods: Retrospective review of patients with HIV and early neurosyphilis in three centres in Melbourne, Australia, in 2000–07. Results: Eighteen male HIV patients met the criteria for diagnosis of early neurosyphilis. Thirteen patients (72.2%) had neurological symptoms: six with headache (33.3%), four with tinnitus (22.2%) and five with impaired vision (27.8%), and one patient each with ataxia, leg weakness and anal discharge with faecal incontinence. Five patients (27.8%) reported no neurological symptoms. All had serum rapid plasma reagin (RPR) titres ≥1 : 32 and all except one had cerebrospinal fluid positive for syphilis fluorescent treponemal antibodies-absorbed. After treatment with 14–15 days of 1.8 g intravenous benzylpenicillin 4-hourly, 12 of 17 patients (71%) demonstrated a four-fold drop in serum RPR titre over 6–12 months and were considered successfully treated. A rise in RPR was noted in three patients during the 12-month follow-up period, suggesting re-infection or recurrence. Conclusion: HIV-infected patients found to have syphilis either because of symptoms or by routine screening should be carefully assessed for neurological, ophthalmic and otological symptoms and signs. A low threshold for a diagnostic lumbar puncture to exclude the diagnosis of neurosyphilis enables appropriate administration and dose of penicillin for treatment, which appears successful in ~75% of cases.
Publisher: Oxford University Press (OUP)
Date: 05-07-2017
DOI: 10.1093/CID/CIX598
Publisher: Oxford University Press (OUP)
Date: 06-2019
DOI: 10.1093/MMY/MYY165
Abstract: Invasive fungal infections (IFIs) occur predominantly in immunocompromised in iduals but can also be seen in previously well persons. The human innate immune system recognizes key components of the fungal cell wall as foreign resulting in a myriad of signaling cascades. This triggers release of antifungal molecules as well as adaptive immune responses, which kill or at least contain the invading fungi. However, these defences may fail in hosts with primary or secondary immunodeficiencies resulting in IFIs. Knowledge of a patient's immune status enables the clinician to predict the fungal infections most likely to occur. Moreover, the occurrence of an opportunistic mycosis in a patient without known immunocompromise usually should prompt a search for an occult immune defect. A rapidly expanding number of primary and secondary immunodeficiencies associated with mycoses has been identified. An investigative approach to determining the nature of these immunodeficiencies is suggested to help guide clinicians encountering patients with IFI. Finally, promising adjunctive immunotherapy measures are currently being investigated in IFI.
Publisher: Elsevier BV
Date: 05-2017
Publisher: MDPI AG
Date: 23-12-2015
DOI: 10.3390/JOF2010001
Publisher: American Medical Association (AMA)
Date: 09-04-2019
Publisher: Oxford University Press (OUP)
Date: 15-10-2013
DOI: 10.1093/CID/CIT476
Publisher: Elsevier BV
Date: 12-2015
Publisher: John Wiley & Sons, Ltd
Date: 18-10-2006
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.DIAGMICROBIO.2014.09.006
Abstract: We determined the susceptibility of 102 clinical isolates Cryptococcus neoformans from Durban, South Africa, to hotericin B, fluconazole, flucytosine, and voriconazole using broth microdilution (BMD) according to the Clinical and Laboratory Standards Institute M27-A3 document and compared these results with Etest and Vitek 2(®). Essential agreement (EA) of Etest and Vitek 2(®) compared to BMD was determined. Low MICs that were below the epidemiological cutoff values of the 4 antifungal agents tested were demonstrated by all isolates. The EA of Etests for fluconazole, hotericin, and voriconazole was 95.1%, 83.3%, and 91.2%, respectively, and for Vitek 2(®) EA for fluconazole, hotericin, and flucytosine was 97.1%, 95.1%, and 97.1%, respectively. The Vitek 2(®) showed good agreement with BMD and is a suitable alternative. Etests demonstrated good EA for azoles only. Clinical cryptococcal isolates from Durban remain susceptible to current recommended antifungal therapy.
Publisher: CSIRO Publishing
Date: 2014
DOI: 10.1071/MA14023
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.1093/OFID/OFX032
Abstract: We measured human immunodeficiency virus (HIV) ribonucleic acid (RNA) in paired cerebrospinal fluid (CSF) and plasma s les in a prospective study of 91 HIV-infected, antiretroviral therapy-naive patients with cryptococcal meningitis. Cerebrospinal fluid HIV RNA was lower than in plasma (median 4.7 vs 5.2 log10 copies/mL, P & .0001) and positively correlated with plasma HIV RNA, peripheral CD4+ T-cell percentage, and CSF CXCL10. Plasma/CSF ratio of HIV RNA ranged widely from 0.2 to 265.5 with a median of 2.6. Cerebrospinal fluid quantitative cryptococcal culture positively correlated with CSF CCL2 and CCL3. CSF-plasma viral discordance was not associated with cryptococcal-associated immune reconstitution inflammatory syndrome.
Publisher: Springer Science and Business Media LLC
Date: 06-09-2021
DOI: 10.1186/S12879-021-06628-0
Abstract: Antimicrobial resistance (AMR) is a significant threat to global public health. Many medical curricula have limited clinical cases and materials focused on AMR, yet enhanced AMR education and training are needed to support antimicrobial stewardship programmes. We used crowdsourcing methods to develop open-access, learner-centred AMR resources. Crowdsourcing is the process of having a large group, including experts and non-experts, solve a problem and then share solutions with the public. We organised a global crowdsourcing contest soliciting AMR-related multiple-choice questions, infographics, and images. First, we convened a erse steering committee group to finalise a call for entries. Second, we launched the contest and disseminated the call for entries using social media, blog posts, email, and an in-person event. Partner institutions included two digital healthcare platforms: Figure 1 ® and Ding Xiang Yuan. Both organizations serve as online communities for healthcare specialists and professionals to report and comment on clinical information. At the end of the call, solicited entries were screened for eligibility and judged on merit and relevance to AMR learning and education. Exceptional entries were recognised, awarded prizes, and further reviewed for sharing with the public via open-access platforms. We received 59 entries from nine countries. These included 54 multiple-choice questions, four infographics, and one image. Eligible entries (n = 56) were reviewed and assigned a score on a 1–10 scale. Eight entries received mean scores greater than 6.0 and were selected as finalists. The eight finalist entries consisted of three infographics and five multiple-choice questions. They were disseminated through open-access publications and online medical communities. Although we launched a global call, we relied heavily on medical student groups and the entries received were not entirely globally representative. We demonstrate that crowdsourcing challenge contests can be used to identify infectious disease teaching materials. Medical educators and curriculum developers can adapt this method to solicit additional teaching content for medical students.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 24-08-2013
Publisher: Springer Science and Business Media LLC
Date: 22-03-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2014
Publisher: Springer Science and Business Media LLC
Date: 08-02-2017
DOI: 10.1007/S00204-016-1916-3
Abstract: The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum. In critically ill patients, it is also recognised that achievement of their pharmacokinetic harmacodynamic targets shows large inter-in idual variability. As a drug class, they are safe to use and are associated with few adverse reactions and few drug-drug interactions of significance. Recent discovery of their ability to prevent and treat Candida biofilm formation particularly in the presence of invasive medical devices and also their ability to penetrate into mucosal surfaces such as vulvovaginal candidiasis has opened up new opportunities for research into their drug delivery. New dosing intervals are being explored to allow less frequent intravenous dosing in the ambulatory setting, and a new long-acting echinocandin, CD101, is being developed for weekly and topical administration.
Publisher: SAGE Publications
Date: 10-10-2021
DOI: 10.1177/17407745211049829
Abstract: Safe and effective therapies for COVID-19 are urgently needed. In order to meet this need, the Accelerating COVID-19 Therapeutic Interventions and Vaccines public–private partnership initiated the Therapeutics for Inpatients with COVID-19. Therapeutics for Inpatients with COVID-19 is a multi-arm, multi-stage platform master protocol, which facilitates the rapid evaluation of the safety and efficacy of novel candidate antiviral therapeutic agents for adults hospitalized with COVID-19. Five agents have so far entered the protocol, with rapid answers already provided for three of these. Other agents are expected to enter the protocol throughout 2021. This protocol contains a number of key design and implementation features that, along with challenges faced by the protocol team, are presented and discussed. Three clinical trial networks, encompassing a global network of clinical sites, participated in the protocol development and implementation. Therapeutics for Inpatients with COVID-19 utilizes a multi-arm, multi-stage design with an agile and robust approach to futility and safety evaluation at 300 patients enrolled, with subsequent expansion to full s le size and an expanded target population if the agent shows an acceptable safety profile and evidence of efficacy. Rapid recruitment to multiple agents is enabled through the sharing of placebo, the confining of agent-specific information to protocol appendices, and modular consent forms. In collaboration with the Food and Drug Administration, a thorough safety data collection and Data and Safety Monitoring Board schedule was developed for the study of potential therapeutic agents with limited in-human data in hospitalized patients with COVID-19. As of 8 August 2021, five agents have entered the Therapeutics for Inpatients with COVID-19 master protocol and a total of 1909 participants have been randomized to one of these agents or matching placebo. There were a number of challenges faced by the study team that needed to be overcome in order to successfully implement Therapeutics for Inpatients with COVID-19 across a global network of sites. These included ensuring drug supply and reliable recruitment allowing for changing infection rates across the global network of sites, the need to balance the collection of data and s les without overburdening clinical staff and obtaining regulatory approvals across a global network of sites. Through a robust multi-network partnership, the Therapeutics for Inpatients with COVID-19 protocol has been successfully used across a global network of sites for rapid generation of efficacy data on multiple novel antiviral agents. The protocol design and implementation features used in this protocol, and the approaches to address challenges, will have broader applicability. Mechanisms to facilitate improved communication and harmonization among country-specific regulatory bodies are required to achieve the full potential of this approach in dealing with a global outbreak.
Publisher: Wiley
Date: 12-2014
DOI: 10.1111/IMJ.12601
Abstract: Healthcare-associated fungal outbreaks impose a substantial economic burden on the health system and typically result in high patient morbidity and mortality, particularly in the immunocompromised host. As the population at risk of invasive fungal infection continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ preventative measures has become increasingly important. These guidelines outline the standard quality processes hospitals need to accommodate into everyday practice and at times of healthcare-associated outbreak, including the role of antifungal stewardship programmes and best practice environmental s ling. Specific recommendations are also provided to help guide the planning and implementation of quality processes and enhanced surveillance before, during and after high-risk activities, such as hospital building works. Areas in which information is still lacking and further research is required are also highlighted.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15592
Abstract: Invasive fungal disease (IFD) due to moulds other than Aspergillus is a significant cause of mortality in patients with malignancies or post haemopoietic stem cell transplantation. The current guidelines focus on the diagnosis and management of the common non‐ Aspergillus moulds (NAM), such as Mucorales, Scedosporium species (spp.), Lomentospora prolificans and Fusarium spp. Rare but emerging NAM including Paecilomyces variotii , Purpureocillium lilacinum and Scopulariopsis spp. are also reviewed. Culture and histological examination of tissue biopsy specimens remain the mainstay of diagnosis, but molecular methods are increasingly being used. As NAM frequently disseminate, blood cultures and skin examination with biopsy of any suspicious lesions are critically important. Treatment requires a multidisciplinary approach with surgical debridement as a central component. Other management strategies include control of the underlying disease redisposing factors, augmentation of the host response and the reduction of immunosuppression. Carefully selected antifungal therapy, guided by susceptibility testing, is critical to cure. We also outline novel antifungal agents still in clinical trial which offer substantial potential for improved outcomes in the future. Paediatric recommendations follow those of adults. Ongoing epidemiological research, improvement in diagnostics and the development of new antifungal agents will continue to improve the poor outcomes that have been traditionally associated with IFD due to NAM.
Publisher: American Thoracic Society
Date: 15-09-2022
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15593
Abstract: 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.
Publisher: Oxford University Press (OUP)
Date: 09-04-2022
DOI: 10.1093/CID/CIAC249
Abstract: Identifying factors that determine the frequency of latently infected CD4+ T cells on antiretroviral therapy (ART) may inform strategies for human immunodeficiency virus (HIV) cure. We investigated the role of CD4+ count at ART initiation for HIV persistence on ART. Among participants of the Strategic Timing of Antiretroviral Treatment Study, we enrolled people with HIV (PWH) who initiated ART with CD4+ T-cell counts of 500–599, 600–799, or ≥ 800 cells/mm3. After 36–44 months on ART, the levels of total HIV-DNA, cell-associated unspliced HIV-RNA (CA-US HIV-RNA), and two-long terminal repeat HIV-DNA in CD4+ T cells were quantified and plasma HIV-RNA was measured by single-copy assay. We measured T-cell expression of Human Leucocyte Antigen-DR Isotype (HLA-DR), programmed death-1, and phosphorylated signal transducer and activator of transcription-5 (pSTAT5). Virological and immunological measures were compared across CD4+ strata. We enrolled 146 PWH, 36 in the 500–599, 60 in the 600–799, and 50 in the ≥ 800 CD4 strata. After 36–44 months of ART, total HIV-DNA, plasma HIV-RNA, and HLA-DR expression were significantly lower in PWH with CD4+ T-cell count ≥ 800 cells/mm3 at ART initiation compared with 600–799 or 500–599 cells/mm3. The median level of HIV-DNA after 36–44 months of ART was lower by 75% in participants initiating ART with ≥ 800 vs 500–599 cells/mm3 (median [interquartile range]: 16.3 [7.0–117.6] vs 68.4 [13.7–213.1] copies/million cells, respectively). Higher pSTAT5 expression significantly correlated with lower levels of HIV-DNA and CA-US HIV-RNA. Virological measures were significantly lower in females. Initiating ART with a CD4+ count ≥ 800 cells/mm3 compared with 600–799 or 500–599 cells/mm3 was associated with achieving a substantially smaller HIV reservoir on ART.
Publisher: Oxford University Press (OUP)
Date: 16-07-2018
Abstract: Initiation of antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-infected in iduals with cryptococcal meningitis places them at risk for Cryptococcus-associated immune reconstitution inflammatory syndrome (C-IRIS). The relationship between antibody immunity and C-IRIS risk has not been investigated. We compared plasma levels of immunoglobulins, C. neoformans glucuronoxylomannan (GXM) capsule-specific and laminarin (Lam)-binding IgM and IgG, and percentages of peripheral blood total and memory B cells between 27 HIV-infected patients with CM who developed C-IRIS and 63 who did not, and evaluated associations of these parameters with risk of C-IRIS. Prior to initiation of ART, plasma IgM, Lam-binding IgM (Lam-IgM), Lam-IgG, and GXM-IgM levels were significantly lower in patients who developed C-IRIS than those who did not. Multivariate analysis revealed significant inverse associations between C-IRIS and IgM (P = .0003), Lam-IgM (P = .0005), Lam-IgG (P = .002), and GXM-IgM (P = .002) independent of age, sex, HIV viral load, CD4+ T-cell count, and cerebrospinal fluid fungal burden. There were no associations between C-IRIS and total or memory B cells. Antibody profiles that include plasma IgM, Lam-IgM, Lam-IgG, and/or GXM-IgM may have value in furthering our understanding of C-IRIS pathogenesis and hold promise as candidate biomarkers of C-IRIS risk.
Publisher: Wiley
Date: 11-2021
DOI: 10.1111/IMJ.15591
Abstract: Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID‐19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological‐based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non‐culture methods employing fungal biomarkers in pre‐emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first‐line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological‐based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.
Publisher: Elsevier BV
Date: 08-2023
Publisher: Elsevier BV
Date: 02-2022
Publisher: John Wiley & Sons, Ltd
Date: 17-10-2007
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.PCL.2009.09.003
Abstract: Acute lower respiratory infections (ALRI) are the major cause of morbidity and mortality in young children worldwide. ALRIs are important indicators of the health disparities that persist between Indigenous and non-Indigenous children in developed countries. Bronchiolitis and pneumonia account for the majority of the ALRI burden. The epidemiology, diagnosis, and management of these diseases in Indigenous children are discussed. In comparison with non-Indigenous children in developing countries they have higher rates of disease, more complications, and their management is influenced by several unique factors including the epidemiology of disease and, in some remote regions, constraints on hospital referral and access to highly trained staff. The prevention of repeat infections and the early detection and management of chronic lung disease is critical to the long-term respiratory and overall health of these children.
Publisher: Frontiers Media SA
Date: 29-05-2018
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.MSARD.2019.101923
Abstract: Fingolimod, a sphingosine-1-phosphate modulator used in the treatment of relapsing-remitting multiple sclerosis, has been associated with several cases of cryptococcosis. We present a case of Cryptococcal meningoencephalitis attributable to Cryptococcus neoformans var. grubii, in a 58-year-old bird-keeper from Australia, after 7 years of fingolimod therapy. We discuss this in the context of previously reported cases, our understanding of fingolimod immune modulation, and known Cryptococcus pathobiology. We suggest consideration of harm minimisation behaviours in patients requiring fingolimod, particularly in those with profound CD4 lymphopenia. Furthermore, we echo the call for improved post-marketing surveillance systems to determine the epidemiology of atypical infections with novel immunomodulatory treatments.
Publisher: Oxford University Press (OUP)
Date: 12-06-2013
Publisher: Public Library of Science (PLoS)
Date: 16-11-2011
Publisher: Oxford University Press (OUP)
Date: 07-2018
DOI: 10.1093/OFID/OFY157
Abstract: Paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS) affects ~25% of human immunodeficiency virus (HIV)-infected patients with cryptococcal meningitis (CM) after they commence antiretroviral therapy (ART) resulting in significant morbidity and mortality. Genomic studies in cryptococcal meningitis and C-IRIS are rarely performed. We assessed whole blood transcriptomic profiles in 54 HIV-infected subjects with CM who developed C-IRIS (27) and compared the results with control subjects (27) who did not experience neurological deterioration over 24 weeks after ART initiation. S les were analyzed by whole genome microarrays. The predictor screening algorithms identified the low expression of the components of interferon-driven antiviral defense pathways, such as interferon-inducible genes, and higher expression of transcripts that encode granulocyte-dependent proinflammatory response molecules as predictive biomarkers of subsequent C-IRIS. Subjects who developed early C-IRIS (occurred within 12 weeks of ART initiation) were characterized by upregulation of biomarker transcripts involved in innate immunity such as the inflammasome pathway, whereas those with late C-IRIS events (after 12 weeks of ART) were characterized by abnormal upregulation of transcripts expressed in T, B, and natural killer cells, such as IFNG, IL27, KLRB1, and others. The AIM2, BEX1, and C1QB were identified as novel biomarkers for both early and late C-IRIS events. An inability to mount effective interferon-driven antiviral immune response, accompanied by a systemic granulocyte proinflammatory signature, prior to ART initiation, predisposes patients to the development of C-IRIS. Although early and late C-IRIS have seemingly similar clinical manifestations, they have different molecular phenotypes (as categorized by bioinformatics analysis) and are driven by contrasting inflammatory signaling cascades.
No related grants have been discovered for Christina Catherine Chang.