ORCID Profile
0000-0002-8987-4358
Current Organisation
James Cook University
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Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.AHJ.2007.07.023
Abstract: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies. Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers. The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke. The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.
Publisher: MDPI AG
Date: 15-07-2021
DOI: 10.3390/HEALTHCARE9070901
Abstract: Background: In this study, we aimed to assess the risk factors associated with mortality due to an infectious disease over the short-, medium-, and long-term based on a data-linkage study for patients discharged from an infectious disease unit in North Queensland, Australia, between 2006 and 2011. Methods: Age-sex standardised mortality rates (SMR) for different subgroups were estimated, and the Kaplan-Meier method was used to estimate and compare the survival experience among different groups. Results: Overall, the mortality rate in the hospital cohort was higher than expected in comparison with the Queensland population (SMR: 15.3, 95%CI: 14.9–15.6). The long-term mortality risks were significantly higher for severe infectious diseases than non-infectious diseases for male sex, Indigenous, residential aged care and elderly in iduals. Conclusion: In general, male sex, Indigenous status, age and comorbidity were associated with an increased hazard for all-cause deaths.
Publisher: Oxford University Press (OUP)
Date: 12-2003
DOI: 10.1086/379324
Abstract: When the adaptive immune response is either immature or compromised, the innate immune system constitutes the principle defense against infection. Mannose-binding lectin (MBL) is a C-type serum lectin that plays a central role in the innate immune response. MBL binds microbial surface carbohydrates and mediates opsonophagocytosis directly and by activation of the lectin complement pathway. A wide variety of clinical isolates of bacteria, fungi, viruses, and parasites are bound by MBL. Three polymorphisms in the structural gene MBL2) and 2 promoter gene polymorphisms are commonly found that result in production of low serum levels of MBL. Clinical studies have shown that MBL insufficiency is associated with bacterial infection in patients with neutropenia and meningococcal sepsis. Low MBL levels appear to predispose persons to HIV infection. Numerous other potential infectious disease associations have been described. Therapy to supplement low MBL levels is being explored using either plasma-derived or recombinant material.
Publisher: Oxford University Press (OUP)
Date: 15-02-2009
DOI: 10.1086/596313
Abstract: Mannose-binding lectin (MBL) is an important mediator of innate immunity and is synthesized primarily by the liver. Low MBL levels are common, are due primarily to polymorphisms in the gene encoding MBL (MBL2), and are associated with an increased risk of infection, particularly when immunity is compromised. We report a large, retrospective study that examined the association between MBL status and clinically significant infection following orthotopic liver transplantation. One hundred two donor-recipient orthotopic liver transplantation pairs were studied. Five polymorphisms in the promoter and coding regions of MBL2 were examined. MBL levels were measured, using the mannan-binding and C4-deposition assays, in serum s les obtained before and after transplantation. Associations between MBL status, as assessed by serum MBL levels and MBL2 genotype, and time to first clinically significant infection (CSI) after transplantation were examined in survival analysis with consideration of competing risks. The median duration of follow-up after orthotopic liver transplantation was 4 years. Thirty-six percent of recipients developed CSI after transplantation. The presence of MBL2 coding mutations in the donor was significantly associated with CSI in the recipient the cumulative incidence function of infection was 55% in recipients of deficient livers, compared with 32% for recipients of wild-type livers (P = .002). Infection was not associated with recipient MBL2 genotype. Low MBL levels after orthotopic liver transplantation levels (mannan-binding <1 microg/mL or C4 deposition <0.2 C4 U/microL) were also associated with CSI (cumulative incidence function, 52% vs. 20%, P = .003 and cumulative incidence function, 54% vs. 24%, P = .007, respectively). In multivariate analysis, mutation in the MBL2 coding region of the donor (hazard ratio, 2.8 P = .005) and the use of cytomegalovirus prophylaxis (hazard ratio, 2.6 P = .005) were independently associated with CSI. Recipients of MBL-deficient livers have almost a 3-fold greater likelihood of developing CSI and may benefit from MBL replacement.
Publisher: Wiley
Date: 12-2017
DOI: 10.1111/IMJ.13601
Abstract: Currently, treatment of latent tuberculosis infection (LTBI) in Australia consists most commonly of a 9-month course of isoniazid (9H). A 3-month course of weekly isoniazid and rifapentine (3HP) has been shown to be as effective as 9 months of daily isoniazid, and associated with less hepatotoxicity however, rifapentine is not currently available in Australia. Introduction of this regimen would have apparent advantages for people with LTBI in Victoria by safely shortening duration of LTBI therapy. However, the cost benefit of this new therapeutic approach is uncertain. Cost-analysis of standard and short-course therapy for LTBI in an Australian context. Single-centre randomised controlled trial conducted between December 2013-March 2016. Participants underwent 1:1 randomisation to either a 9-month course of daily isoniazid or a 12-week course of weekly isoniazid and rifapentine. The primary outcome measure was total healthcare system costs (in Australian dollars AUD) per completed course of LTBI therapy. Secondary cost analyses were performed to consider varying assumptions regarding commercial cost of rifapentine. Overall, 34 of 40 (85%) participants in the 9H group and 36/40 (90%) in the 3HR group completed therapy. One patient in the 3HP group was hospitalised for a febrile illness no hospitalisations were recorded in the 9H group. The cost per completed course of 9H was 601 AUD, while that of 3HP was significantly lower at 511 AUD (P < 0.01). This study provides cost analysis evidence to support the use of 3HP for the treatment of LTBI in Australia.
Publisher: Public Library of Science (PLoS)
Date: 09-2015
Publisher: BMJ
Date: 2017
Publisher: Oxford University Press (OUP)
Date: 16-10-2012
DOI: 10.1093/CID/CIS878
Abstract: The timing of cardiac surgery after stroke in infective endocarditis (IE) remains controversial. We examined the relationship between the timing of surgery after stroke and the incidence of in-hospital and 1-year mortalities. Data were obtained from the International Collaboration on Endocarditis-Prospective Cohort Study of 4794 patients with definite IE who were admitted to 64 centers from June 2000 through December 2006. Multivariate logistic regression and Cox regression analyses were performed to estimate the impact of early surgery on hospital and 1-year mortality after adjustments for other significant covariates. Of the 857 patients with IE complicated by ischemic stroke syndromes, 198 who underwent valve replacement surgery poststroke were available for analysis. Overall, 58 (29.3%) patients underwent early surgical treatment vs 140 (70.7%) patients who underwent late surgical treatment. After adjustment for other risk factors, early surgery was not significantly associated with increased in-hospital mortality rates (odds ratio, 2.308 95% confidence interval [CI], .942-5.652). Overall, probability of death after 1-year follow-up did not differ between 2 treatment groups (27.1% in early surgery and 19.2% in late surgery group, P = .328 adjusted hazard ratio, 1.138 95% CI, .802-1.650). There is no apparent survival benefit in delaying surgery when indicated in IE patients after ischemic stroke. Further observational analyses that include detailed pre- and postoperative clinical neurologic findings and advanced imaging data (eg, ischemic stroke size), may allow for more refined recommendations on the optimal timing of valvular surgery in patients with IE and recent stroke syndromes.
Publisher: Wiley
Date: 29-05-2020
Publisher: Wiley
Date: 04-2004
DOI: 10.1111/J.1439-0507.2004.00959.X
Abstract: Zygomycosis often requires aggressive surgical and antifungal therapy. We report a non‐neutropenic patient with myelodysplastic syndrome and iron overload receiving cytotoxic therapy who presented with pulmonary Rhizopus oryzae infection. This patient was cured through the use of itraconazole alone and the literature on the utility of azole antifungals for zygomycosis is reviewed.
Publisher: European Respiratory Society (ERS)
Date: 06-2017
DOI: 10.1183/13993003.02098-2016
Abstract: Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers. In this study, we combined an integrated genomic analysis of 1071 in iduals with in vitro experiments using well-established infection models. We identified a single-gene biomarker, IFI27 , which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. In vitro studies showed that IFI27 was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. In vivo studies confirmed that IFI27 was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), IFI27 displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections. IFI27 represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting its implementation may improve the diagnosis and management of respiratory infection.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.IJID.2015.03.006
Abstract: Extended-spectrum beta-lactamase-expressing Gram-negative bacilli (ESBL-GNB) now commonly cause community-acquired infections, including urinary tract infections (UTI), and represent a challenge for practitioners in choosing empirical antibiotics. The aim of this study was to describe the epidemiology and clinical characteristics of UTIs/bacteriuria due to ESBL-GNB in Australia. At a single-site tertiary referral hospital, 100 cases with UTIs/bacteriuria due to ESBL-GNB were matched to 100 cases where UTIs/bacteriuria were caused by organisms matching the ESBL bacterial species that had routine susceptibility to antibiotics. Potential risk factors for ESBL-GNB UTI/bacteriuria and differences in clinical outcomes were identified. Length of admission prior to positive s le (odds ratio (OR) 1.3, p = 0.03, per week), exposure to antibiotics (OR 5.7, p < 0.001), return from overseas travel (OR 6.5, p = 0.002), and nursing home residency (OR 4.2, p = 0.03) were identified as risk factors associated with ESBL-GNB UTI/bacteriuria in the multivariate analysis. In addition, ESBL-GNB-infected cases subsequently had a longer inpatient stay (median 6 vs. 2 days, p = 0.002) and were admitted to the intensive care unit more frequently (28/100 vs. 8/100, p < 0.001). Our results emphasize the need for culture of a mid-stream urine specimen prior to commencing antibacterials, especially in patients with the risk factors identified herein associated with ESBL-GNB UTI/bacteriuria.
Publisher: Springer Science and Business Media LLC
Date: 07-2005
DOI: 10.1007/S10875-005-4702-1
Abstract: Mannose Binding Lectin (MBL) is a liver derived, circulating plasma protein that plays a pivotal role in innate immunity. MBL functions as a pathogen recognition molecule, opsonising organisms and initiating the complement cascade. MBL deficiency arising from mutations and promoter polymorphisms in the MBL2 gene is common and has been associated with risk, severity, and frequency of infection in a number of clinical settings. With MBL therapy on the horizon, the usefulness of replacement MBL therapy has been challenged by the notion, that as an acute phase protein, MBL levels may rise under stress to sufficient levels, in in iduals who are usually deficient. This report demonstrates that in patients with sepsis and septic shock, the majority of patients do not display an MBL acute phase response: 41.4% of in iduals maintained consistent MBL levels throughout hospital stay, 31.3% of in iduals demonstrated a positive acute phase response, and a negative acute phase response was observed in 27.3% of in iduals studied. Importantly, a positive acute phase response was generally observed in in iduals with wild-type MBL2 genes. When a positive acute phase response was observed in in iduals with coding mutation, these in iduals demonstrated a normal MBL level on admission to hospital. Furthermore, no in idual, regardless of genotype who was MBL deficient at admission was able to demonstrate a positive acute phase response into the normal MBL range. These findings indicate MBL demonstrates a variable acute phase response in the clinical setting of sepsis and septic shock.
Publisher: S. Karger AG
Date: 07-07-2010
DOI: 10.1159/000228159
Abstract: Mannose-binding lectin (MBL) is an innate immune system pattern recognition protein that kills a wide range of pathogenic microbes through complement activation. A substantial proportion of all human populations studied to date have MBL deficiency due to i MBL2 /i polymorphisms, which potentially increases susceptibility to infectious disease. MBL binds numerous respiratory pathogens but the capsule of i Streptococcus pneumoniae /i abrogates its efficient binding. Clinical studies in humans have shown that MBL deficiency appears to predispose to severe respiratory tract infection. A recent meta-analysis shows that MBL deficiency was associated with death in patients with pneumococcal infection after adjusting for bacteraemia and comorbidities. Human clinical studies have also shown associations between MBL deficiency and various less common respiratory infections. Intracellular infections like tuberculosis may be less common with MBL deficiency because of reduced opsonophagocytosis. Lung secretions contain small amounts of MBL that are potentially sufficient to activate complement, but their measurement is confounded by dilution inherent in collection techniques. Therefore, if this protein does play a role in pulmonary immunity it is presumably through prevention of haematogenous dissemination of respiratory pathogens while adding to mucosal defences. Ficolins are collectins that are structurally and functionally related to MBL and are either present in serum or expressed in tissues including the lung. Limited variation in serum levels of L- and H-ficolin result from the presence of i FCN2 /i and i FCN3 /i polymorphisms. Initial studies on the impact of i FCN2 /i polymorphisms or low L-ficolin levels do not seem to show major associations with respiratory infection. MBL is being developed as a new immunotherapeutic agent for prevention of infection in immunocompromised hosts. The available literature suggests that it may also be of benefit in MBL deficient patients with severe pneumonia. This review concentrates on clinical associations between MBL deficiency and susceptibility to respiratory tract infection.
Publisher: Oxford University Press (OUP)
Date: 09-04-2014
DOI: 10.1111/CEI.12241
Abstract: Either immune selection or stochastic processes may have influenced the frequency of highly polymorphic genes such as mannose-binding lectin 2 (MBL2). This pattern recognition receptor of the innate immune system recognizes and binds to pathogenic microorganisms and apoptotic cells leading to lectin pathway complement killing or clearance. In almost all of a large number of studies in different ethnic groups worldwide there is 20–25% carriage of low MBL2 haplotypes, with 8–10% of each population having no MBL detectable in the blood. The source of this high variability of MBL2 remains cryptic. It arises from six main snps in the prompter and exon regions of the gene that assort into seven common haplotypes under linkage disequilibrium. While global studies of MBL2 show that it is not under immune selection pressure, these results are not the same when the same population genetic tools are used on large national studies. Other analyses point to the silenced MBL1 pseudogene and development of promoter polymorphisms in humans as evidence of selection pressure favouring low-producing haplotypes. While these analyses cannot be reconciled readily, there are two processes by which MBL heterozygosity could have been advantageous in an evolutionary sense protection against adverse effects of various infectious diseases and lethal manifestations of atherosclerosis – a disease that now seems to have a more ancient history than assumed previously. Ultimately, consideration of the context for possible future therapeutic manipulation of MBL means that this can proceed independently of resolution of the evolutionary forces that have shaped MBL2 polymorphism.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2012
Publisher: Wiley
Date: 29-06-2011
DOI: 10.1111/J.1442-9071.2011.02572.X
Abstract: Mannose-binding lectin plays a central effector role in the lectin pathway of complement activation. Frequently occurring MBL2 polymorphisms result in mannose-binding lectin deficiency, which increases susceptibility to infection. We characterized mannose-binding lectin levels and function in non-inflamed and inflamed human eyes, and evaluated its relationship to blood mannose-binding lectin levels and function. Prospective, observational clinical study with controls and cases. Twenty-seven patients with paired blood and ocular s les (aqueous and/or vitreous) including 15 controls (non-inflamed) and 12 cases (inflamed). Blood and ocular s les were collected from controls (n = 15) with quiet eyes during elective cataract surgery and cases with inflamed eyes including proven/suspected endophthalmitis (n = 11) and herpetic retinal vasculitis (n = 1). Mannan-binding and C4 deposition enzyme-linked quantify mannose-binding lectin levels and function. Blood and ocular mannose-binding lectin levels and function. Of 27 patients, 10 (37%) were mannose-binding lectin-deficient (defined as blood mannose-binding lectin levels <500 ng/mL). Blood mannose-binding lectin levels (P= 0.16) or function (P= 0.43) were not significantly different between controls and cases. As expected, there was a high correlation between blood mannose-binding lectin levels and function (r(2) = 0.74). However, there was significantly more mannose-binding lectin in inflamed eyes than non-inflamed eyes measured as level (P < 0.01) or C4 deposition function (P < 0.01). Our study demonstrated that mannose-binding lectin is significantly elevated in inflamed human eyes but virtually undetectable in non-inflamed control eyes, suggesting a role in sight-threatening ocular inflammation.
Publisher: MDPI AG
Date: 29-01-2023
DOI: 10.3390/MICROORGANISMS11020336
Abstract: Reference genes are frequently used for the normalization of quantitative reverse transcriptase PCR (qRTPCR) data in gene expression studies. Staphylococcus aureus is one of the most common causes of biofilm-related infections. Savirin and ticagrelor show in vitro as well as in vivo antibiofilm activity against S. aureus. The main aim of this study was to identify the most stably expressed reference genes to study the effect of these molecules on genes in a strong biofilm producing S. aureus isolate isolated from biofilm-related infection. Quantitative real-time PCR was performed by using relative quantification method. Four different algorithms, delta Ct, normfinder, bestkeeper, and genorm, followed by a comprehensive analysis was used to identify the most stable reference genes from a list of sixteen different candidate reference genes. All four algorithms reported different results, with some comparable findings among some methods. In the comprehensive analysis of the results of all the algorithms used, the most stable reference genes found were spa, rpoD, and pyk for savirin treatment experiment and gapdH, gyrA, and gmk for ticagrelor treatment experiment. The optimal number of reference genes required was two for both the experimental conditions. Despite having some drawbacks, each algorithm can reliably determine an appropriate reference gene independently. However, based on consensus ranking and the required optimal number of reference genes reported, spa and rpoD were the most appropriate reference genes for savirin treatment experiment, and gapdH and gyrA were most appropriate for ticagrelor treatment experiment. This study provides baseline data on reference genes to study the effect of savirin or ticagrelor treatment on the expression of potential reference genes in S. aureus. We recommend prior re-validation of reference genes on a case-by-case basis before they can be used.
Publisher: Springer Science and Business Media LLC
Date: 18-11-2014
Publisher: Elsevier BV
Date: 08-2002
Publisher: Elsevier BV
Date: 06-2009
Publisher: Oxford University Press (OUP)
Date: 12-05-2015
DOI: 10.1093/CID/CIV380
Publisher: Oxford University Press (OUP)
Date: 19-08-2010
DOI: 10.1111/J.1365-2249.2010.04221.X
Abstract: It has been proposed that mannose-binding lectin (MBL) levels may impact upon host susceptibility to tuberculosis (TB) infection however, evidence to date has been conflicting. We performed a literature review and meta-analysis of 17 human trials considering the effect of MBL2 genotype and/or MBL levels and TB infection. No significant association was demonstrated between MBL2 genotype and pulmonary TB infection. However, the majority of studies did not report MBL2 haplotype inclusive of promoter polymorphisms. Serum MBL levels were shown to be consistently elevated in the setting of TB infection. While this may indicate that high MBL levels protect against infection with TB, the increase was also of a degree consistent with the acute-phase reaction. This analysis suggests that the relatively poorly characterized MBL2 genotypes reported are not associated significantly with susceptibility to pulmonary TB infection, but high MBL serum levels may be.
Publisher: Springer Science and Business Media LLC
Date: 20-02-2014
Publisher: Oxford University Press (OUP)
Date: 11-2006
Publisher: Springer Science and Business Media LLC
Date: 25-10-2007
DOI: 10.1007/S10096-007-0406-1
Abstract: Leptotrichia species typically colonize the oral cavity and genitourinary tract. We report the first two cases of endocarditis secondary to L. goodfellowii sp. nov. Both cases were identified using 16S rRNA gene sequencing. Review of the English literature revealed only two other cases of Leptotrichia sp. endocarditis.
Publisher: Elsevier BV
Date: 08-2014
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.TUBE.2018.08.011
Abstract: Accurate and timely diagnosis of tuberculosis (TB) is essential to control the global pandemic. Currently available immunodiagnostic tests cannot discriminate between latent tuberculosis infection (LTBI) and active tuberculosis. This study aimed to determine whether candidate mycobacterial antigen-stimulated cytokine biomarkers can discriminate between TB-uninfected and TB-infected adults, and additionally between LTBI and active TB disease. 193 adults were recruited, and categorised into four unambiguous diagnostic groups: microbiologically-proven active TB, LTBI, sick controls (non-TB lower respiratory tract infections) and healthy controls. Whole blood assays were used to determine mycobacterial antigen (CFP-10, ESAT-6, PPD)-stimulated cytokine (IL-1ra, IL-2, IL-10, IL-13, TNF-α, IFN-γ, IP-10 and MIP-1β) responses, measured by Luminex multiplex immunoassay. The background-corrected mycobacterial antigen-stimulated cytokine responses of all eight cytokines were significantly higher in TB-infected participants compared with TB-uninfected in iduals, with IL-2 showing the best performance characteristics. In addition, mycobacterial antigen-stimulated responses with IL-1ra, IL-10 and TNF-α were higher in participants with active TB compared those with LTBI, reaching statistical significance with PPD stimulation, although there was a degree of overlap between the two groups. Mycobacterial antigen-stimulated cytokine responses may prove useful in future immunodiagnostic tests to discriminate between tuberculosis-infected and tuberculosis-uninfected in idual, and potentially between LTBI and active tuberculosis.
Publisher: MDPI AG
Date: 09-2021
DOI: 10.3390/ANTIBIOTICS10091060
Abstract: Staphylococcus aureus frequently causes community- and hospital-acquired infections. S. aureus attachment followed by biofilm formation on tissues and medical devices plays a significant role in the establishment of chronic infections. Staphylococcal biofilms encase bacteria in a matrix and protect the cells from antimicrobials and the immune system, resulting in infections that are highly resistant to treatment. The biology of biofilms is complex and varies between organisms. In this review, we focus our discussion on S. aureus biofilms and describe the stages of their formation. We particularly emphasize genetic and biochemical processes that may be vulnerable to novel treatment approaches. Against this background, we discuss treatment strategies that have been successful in animal models of S. aureus biofilm-related infection and consider their possible use for the prevention and eradication of biofilm-related S. aureus prosthetic joint infection.
Publisher: AMPCo
Date: 28-06-2020
DOI: 10.5694/MJA2.50688
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.JINF.2017.04.011
Abstract: A biomarker indicating successful tuberculosis (TB) therapy would assist in determining appropriate length of treatment. This study aimed to determine changes in mycobacteria-specific antigen-induced cytokine biomarkers in patients receiving therapy for latent or active TB, to identify biomarkers potentially correlating with treatment success. A total of 33 adults with active TB and 36 with latent TB were followed longitudinally over therapy. Whole blood stimulation assays using mycobacteria-specific antigens (CFP-10, ESAT-6, PPD) were done on s les obtained at 0, 1, 3, 6 and 9 months. Cytokine responses (IFN-γ, IL-1ra, IL-2, IL-10, IL-13, IP-10, MIP-1β, and TNF-α) in supernatants were measured by Luminex xMAP immunoassay. In active TB cases, median IL-1ra (with CFP-10 and with PPD stimulation), IP-10 (CFP-10, ESAT-6), MIP-1β (ESAT-6, PPD), and TNF-α (ESAT-6) responses declined significantly over the course of therapy. In latent TB cases, median IL-1ra (CFP-10, ESAT-6, PPD), IL-2 (CFP-10, ESAT-6), and IP-10 (CFP-10, ESAT-6) responses declined significantly. Mycobacteria-specific cytokine responses change significantly over the course of therapy, and their kinetics in active TB differ from those observed in latent TB. In particular, mycobacteria-specific IL-1ra responses are potential correlates of successful therapy in both active and latent TB.
Publisher: Springer Science and Business Media LLC
Date: 2014
DOI: 10.1186/CC13787
Publisher: Oxford University Press (OUP)
Date: 15-08-2008
DOI: 10.1086/590006
Publisher: Public Library of Science (PLoS)
Date: 02-04-2013
Publisher: Elsevier BV
Date: 08-2010
Publisher: Mary Ann Liebert Inc
Date: 02-2007
DOI: 10.1089/SUR.2006.093
Publisher: Oxford University Press (OUP)
Date: 11-04-2007
DOI: 10.1111/J.1365-2249.2007.03390.X
Abstract: Innate immune system deficiency may predispose to severe infections such as Legionnaires' disease. We have investigated the role of mannose-binding lectin (MBL) deficiency in the Melbourne Aquarium Legionnaires' disease outbreak. Serum s les from patients and controls that were exposed but shown to be uninfected from the Melbourne Aquarium Legionnaires' disease outbreak were tested for MBL function (C4 deposition) and level (mannan-binding). MBL function was lower in Legionnaires' disease cases than in age- and sex-matched uninfected, exposed controls. The frequency of MBL deficiency with C4 deposition & 0·2 U/µl was significantly higher in Legionnaires' disease cases than in controls. This also applied to Legionnaires' disease cases requiring hospital care. There was no difference in MBL mannan-binding levels between Legionnaires' disease patients and controls. There was no significant interval change in MBL function or level after a mean of 46 days. MBL complement activation functional deficiency appears to predispose to Legionnaires' disease.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JOCN.2012.08.017
Abstract: This report describes an unusual fungal infection of an intrathecal baclofen pump which, to our knowledge, has not been reported previously. We describe a 39-year-old man with severe lower limb spasticity due to secondary progressive multiple sclerosis that was managed with insertion of an intrathecal baclofen pump. He subsequently presented with distinct neurological decline secondary to an intrathecal baclofen pump infection with Aspergillus terreus.
Publisher: American Society of Tropical Medicine and Hygiene
Date: 09-01-2013
Publisher: Oxford University Press (OUP)
Date: 05-2008
DOI: 10.1086/587181
Publisher: Elsevier BV
Date: 03-2000
DOI: 10.1016/S0264-410X(99)00444-2
Abstract: A placebo controlled, randomised, double blind trial was conducted in human volunteers to test a mixture of three recombinant Plasmodium falciparum blood stage antigens for its ability to reduce the initial growth rates of parasites. The vaccine contained recombinant MSP2 (3D7 allele), a portion of MSP1 (190LCS.T3) and part of the RESA antigen (C terminal 771 amino acids) in the Montanide ISA 720 adjuvant (SEPPIC). Twelve volunteers received two doses of the vaccine, 6 weeks apart. The five participants in the placebo group received an equivalent volume of the adjuvant emulsion using the same schedule. Antibody responses were low, as has been reported in earlier studies with this combination, while T cell responses were stronger. All the volunteers were challenged with approximately 140 ring infected red cells of the 3D7 cloned line, 4 weeks after the second dose. Parasitaemia was determined once daily from day 4 using a sensitive and quantitative PCR assay. All the volunteers were infected and were treated on day 8, before any developed symptoms. There was no significant difference in initial parasite growth rates between the verum and placebo groups, nor was there any significant correlation between parasite growth rates and any of the measured immunological responses. These results suggest that the formulation tested in this trial did not generate immune responses that were strong enough to reduce parasite growth in naive volunteers.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1071/HI03129
Publisher: Wiley
Date: 03-2015
DOI: 10.1111/NEP.12423
Abstract: A middle-aged man received a kidney transplant from a deceased multi-organ donor. The recipient suffered cardiac arrest several days post-operatively and sustained hypoxic brain injury and was declared brain dead. Following the family's consent, the allograft kidney was retrieved and re-transplanted into a man with end-stage renal failure secondary to reflux nephropathy. The liver was not transplanted due to suspicion of fatty changes based on macroscopic appearance. After transplantation of other organs, liver histology revealed coagulative parenchymal necrosis with nuclear inclusions and moderate parenchymal cholestasis, suggestive of herpes viral hepatitis. Renal implantation biopsy showed histiocytes with enlarged nuclei containing viral inclusions in the capsular fibrous tissue, with positive immunostaining for herpes simplex virus (HSV). Anti-viral therapy was commenced immediately after obtaining histological evidence of donor HSV infection. Our recipient had pre-formed immunoglobulin G antibodies to HSV-1 and HSV-2, and was immunoglobulin M negative pre-transplant. HSV viraemia was detected day 5 post-transplant with a viral load of 7688 copies/mL by polymerase chain reaction assay. The recipient completed a 30 day course of intravenous ganciclovir before switching to oral valganciclovir as standard cytomegalovirus prophylaxis. The HSV polymerase chain reaction became undetectable on day 7 of intravenous ganciclovir and has remained undetectable. The patient remains well 9 months post-transplant with an estimated glomerular filtration rate of 61 mL/min per 1.73 m(2). Although renal allograft re-use has been shown to be technically possible with a good outcome in this recipient, this does raise issues including assessment of allografts that have undergone repeated severe ischaemic insults and the potential of transmission of infections.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.IJCARD.2014.10.125
Abstract: Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality. Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement. Patients who received bioprostheses were older (62 vs 54years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%) proportion of health care-associated IE was higher (26% vs 17%) intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p=0.0009) and 25.3% vs 16.6% (p<.0001), respectively. In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60). Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298). Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.
Publisher: Public Library of Science (PLoS)
Date: 27-09-2013
Publisher: Elsevier BV
Date: 04-2005
DOI: 10.1016/J.VACCINE.2004.09.040
Abstract: A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 microg, 20 microg or 80 microg of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study.
Publisher: Springer Science and Business Media LLC
Date: 05-07-2006
Publisher: Oxford University Press (OUP)
Date: 12-2008
DOI: 10.1086/593107
Publisher: Oxford University Press (OUP)
Date: 05-2009
DOI: 10.1086/597827
Abstract: Interstitial cystitis causes disabling bladder pain and is usually diagnosed in the absence of infection. We describe a patient with interstitial cystitis who had high urinary levels of polyomavirus that decreased dramatically after initiation of intravesical cidofovir treatment the patient also showed substantial improvement in symptoms. Another patient had milder symptoms of cystitis and intermittent polyomavirus shedding. Polyomaviruses, particularly BK virus, may cause some cases of interstitial cystitis.
Publisher: Public Library of Science (PLoS)
Date: 24-07-2015
Publisher: Elsevier BV
Date: 07-2017
Publisher: Oxford University Press (OUP)
Date: 15-11-2009
DOI: 10.1086/644782
Publisher: Elsevier BV
Date: 2002
Publisher: Public Library of Science (PLoS)
Date: 17-05-2013
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.JINF.2009.03.006
Abstract: To assess the influence of acetyl-salicylic acid (ASA) on clinical outcomes in Staphylococcus aureus infective endocarditis (SA-IE). The International Collaboration on Endocarditis - Prospective Cohort Study database was used in this observational study. Multivariable analysis of the SA-IE cohort compared outcomes in patients with and without ASA use, adjusting for other predictive variables, including: age, diabetes, hemodialysis, cancer, pacemaker, intracardiac defibrillator and methicillin resistance. Data were analysed from 670 patients, 132 of whom were taking ASA at the time of SA-IE diagnosis. On multivariable analysis, ASA usage was associated with a significantly decreased overall rate of acute valve replacement surgery (OR 0.58 [95% CI 0.35-0.97] p<0.04), particularly where valvular regurgitation, congestive heart failure or periannular abscess was the indication for such surgery (OR 0.46 [0.25-0.86] p<0.02). There was no reduction in the overall rates of clinically apparent embolism with prior ASA usage, and no increase in hemorrhagic strokes in ASA-treated patients. In this multinational prospective observational cohort, recent ASA usage was associated with a reduced occurrence of acute valve replacement surgery in SA-IE patients. Future investigations should focus on ASA's prophylactic and therapeutic use in high-risk and newly diagnosed patients with SA bacteremia and SA-IE, respectively.
Publisher: Elsevier BV
Date: 12-2013
Publisher: Oxford University Press (OUP)
Date: 09-03-2015
Publisher: Bentham Science Publishers Ltd.
Date: 2004
Abstract: Vaccines have been described as "weapons of mass protection". The eradication of many diseases is testament to their utility and effectiveness. Nevertheless, many vaccine preventable diseases remain prevalent because of political and economic barriers. Additionally, the effects of immaturity and old age, therapies that incapacitate the adaptive immune system and the multitude of strategies evolved by pathogens to evade immediate or sustained recognition by the mammalian immune system are barriers to the effectiveness of existing vaccines or development of new vaccines. In the front line of defence against the pervasiness of infection are the elements of the innate immune system. Innate immunity is under studied and poorly appreciated. However, in the first days after entry of a pathogen into the body, our entire protective response is dependant upon the various elements of our innate immune repertoire. In spite of its place as our initial defence against infection, attention is only now turning to strategies which enhance or supplement innate immunity. This review examines the need for and potential of innate immune therapies.
Publisher: Oxford University Press (OUP)
Date: 03-1999
Publisher: Elsevier BV
Date: 05-2011
Publisher: Oxford University Press (OUP)
Date: 2008
DOI: 10.1080/13693780701874515
Abstract: While most patients with cryptococcosis have obvious cellular immune deficiency, a minority have no apparent predisposing factors. However, in the latter there may be subtle innate immune system deficiencies which go unrecognized. Mannose-binding lectin (MBL) deficiency is associated with increased susceptibility to infectious diseases and may predispose to cryptococcosis, particularly when it disseminates to the central nervous system (CNS) in apparently immunocompetent patients. MBL function and levels, as well as MBL2 genotype were determined in 36 HIV-negative cryptococcosis patients (25 with CNS involvement) using C4 deposition and mannan-binding ELISA. MBL deficiency was defined using C4 deposition level < 0.2 U/microl or mannan-binding level < 0.5 microg/ml. MBL results were compared between patients with cryptococcosis and healthy controls and among the cryptococcosis patients according to the site of their disease. There was no difference in MBL function, mannan-binding level or increase in the frequency of MBL deficiency or low producing MBL2 genotypes in any of these comparisons. Patients with CNS cryptococcosis were no more likely to be MBL deficient than those with non-CNS disease. It appears that MBL deficiency is not associated with cryptococcosis in non-immunocompromised hosts. Beta errors consequent on the small number of patients studied may account for the lack of association.
Publisher: Wiley
Date: 23-11-2011
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1998
DOI: 10.1097/00002030-199812000-00011
Abstract: To describe two cases of cryptococcal meningitis and one re-exacerbation of Cryptococcus-associated meningitis occurring in temporal association with commencement of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection (CD4 cells 2-4 log10 reduction) HIV viral loads (two out of three patients), and (iii) prominent inflammatory changes in cerebrospinal fluid (white blood cells > 10 x 10(6)/l) at diagnosis (two out of three patients). Our report suggests that in patients with advanced HIV infection, partial immune restitution induced by HAART can precipitate onset of clinically apparent meningitis in those patients with latent cryptococcal central nervous system infection or with residual cryptococcal antigen present in the cerebrospinal fluid.
Publisher: Springer Science and Business Media LLC
Date: 12-2011
DOI: 10.1038/NM.2588
Publisher: American Society for Microbiology
Date: 12-2007
DOI: 10.1128/IAI.00327-07
Abstract: The immune response against the Plasmodium falciparum variant surface antigen P. falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against falciparum malaria. In this study, we used sera from human volunteers who had been infected with the P. falciparum 3D7 strain to investigate the development, specificity, and dynamics of anti-PfEMP1 antibodies measured against six different strain 3D7 Duffy binding-like domain 1α (DBL1α) fusion proteins. We observed that a parasitemia of 20 to 200 infected erythrocytes per μl was required to trigger an antibody response to DBL1α and that antibodies against one DBL1α variant cross-react with other DBL1α variants. Both serum and purified immunoglobulin Gs (IgGs) were able to agglutinate infected erythrocytes, and purified anti-DBL1α IgGs bound to the live infected red blood cell surface in a punctate surface pattern, confirming that the IgGs recognize native PfEMP1. Analysis of sera from tourists naturally infected with P. falciparum suggests that the anti-PfEMP1 antibodies often persisted for more than 100 days after a single infection. These results help to further our understanding of the development of acquired immunity to P. falciparum infections.
Publisher: Wiley
Date: 02-2012
Publisher: Elsevier BV
Date: 12-2015
Publisher: Oxford University Press (OUP)
Date: 10-11-2014
DOI: 10.1093/CID/CIU871
Publisher: Public Library of Science (PLoS)
Date: 28-11-2017
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-03-2010
DOI: 10.1161/CIRCULATIONAHA.109.864488
Abstract: Background— The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. Methods and Results— Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] −5.9%, P .001). With a combined instrument, the instrumental-variable–adjusted ARR in mortality associated with early surgery was −11.2% ( P .001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR −10.9% for quintiles 4 and 5, P =0.002) and those with paravalvular complications (ARR −17.3%, P .001), systemic embolization (ARR −12.9%, P =0.002), S aureus NVE (ARR −20.1%, P .001), and stroke (ARR −13%, P =0.02) but not those with valve perforation or congestive heart failure. Conclusions— Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.
Publisher: Springer Science and Business Media LLC
Date: 25-04-2012
DOI: 10.1007/S00134-012-2570-8
Abstract: Acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) may have potential as adjunctive agents for sepsis. This review considers the large body of literature that indicates a basis for sepsis therapy with ASA and suggests an agenda for future intervention studies in sepsis prevention and treatment. ASA and NSAIDs have beneficial effects in numerous experimental models of sepsis. Low doses of ASA of 100 mg/day or less trigger synthesis of lipoxins that are anti-inflammatory and aid in resolution of inflammation. Higher doses of ASA and NSAIDs act to reduce NF-κB stimulation and inhibit numerous septic pathways. While a previous randomised controlled trial of ibuprofen failed to show a reduction in mortality in sepsis, it did reduce clinical manifestations of sepsis. More recent observational studies have shown reduction in sepsis or acute lung injury leading to lower mortality in ICU patients treated with ASA. Low-dose ASA appears to be beneficial in the prevention and treatment of sepsis and SIRS. If proven, this intervention would have a major, cost-effective impact on sepsis care.
Publisher: Elsevier BV
Date: 05-1999
Publisher: Oxford University Press (OUP)
Date: 30-08-2013
Publisher: Oxford University Press (OUP)
Date: 28-03-2013
DOI: 10.1093/CID/CIT183
Publisher: Informa UK Limited
Date: 10-2014
DOI: 10.2147/DHPS.S68837
Publisher: Elsevier BV
Date: 2002
DOI: 10.1016/S0732-8893(01)00310-8
Abstract: Adult patients with hematologic malignancies along with HIV infected patients were prospectively studied to determine the performance of urine D-arabinitol/L-arabinitol (DA/LA) ratio in diagnosing invasive candidiasis. Ten evaluable febrile neutropenic patients had proven invasive candidiasis and elevated DA/LA ratios were found in 5. Invasive candidiasis with normal DA/LA ratios was most frequently due to Candida krusei infection. This Candida species is a non-producer of arabinitol. Only 4 of 81 febrile neutropenic patients given either antifungal prophylaxis or empiric antifungal treatment had elevated DA/LA ratios. Only 1 of 15 HIV positive patients with either oropharyngeal or esophageal candidiasis had elevated DA/LA ratios. Widespread use of fluconazole prophylaxis in bone marrow transplantation patients at the study hospital has led to an increased prevalence of C. krusei infection. This is the likely reason for the low sensitivity of the test in proven and suspected invasive Candida infections reported here.
Publisher: Oxford University Press (OUP)
Date: 02-2010
DOI: 10.1086/650462
Abstract: . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G(2) (IgG(2)) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection. Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random s le of healthy pregnant women. Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P < .001), anemia (P < .001), and low levels of total IgG (P= .01), IgG(1) (P= .022), and IgG(2) (15 of 19 vs 5 of 20 P= .001 mean value +/- standard deviation [SD], 1.8 +/- 1.7 g/L vs 3.4 +/- 1.4 g/L P= .003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P= .02) and low mean IgG(2) levels (P= .043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG(2)-deficient patients at a mean (+/- SD) of 90 +/- 23 days (R, 38-126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG(2) deficient. Among 17 healthy pregnant control subjects, mildly low IgG(1) and/or IgG(2) levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG(2) (P= .001). Severe H1N1 infection is associated with IgG(2) deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG(2) level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG(2) deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2017
DOI: 10.1097/CCM.0000000000002654
Abstract: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. Fifteen studies described hospital-based cohorts ( n = 17,065), whereas one was a large insurance-based database ( n = 683,421). In idual-level patient data were incorporated from all selected studies. Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. Use of aspirin was associated with a 7% (95% CI, 2–12% p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity ( I 2 = 61.6%). These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.
Start Date: 2013
End Date: 2017
Funder: National Health and Medical Research Council
View Funded ActivityStart Date: 2009
End Date: 2010
Funder: National Health and Medical Research Council
View Funded Activity