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Staphylococcus aureus is among the leading causes of bacterial infections worldwide. The pathogenicity and establishment of S. aureus infections are tightly linked to its ability to modulate host immunity. Persistent infections are often associated with mutant staphylococcal strains that have decreased susceptibility to antibiotics; however, little is known about how these mutations influence bacterial interaction with the host immune system. Here, we discovered that clinical S. aureus isolates activate human monocytes, leading to cell-surface expression of immune stimulatory natural killer group 2D (NKG2D) ligands on the monocytes. We found that expression of the NKG2D ligand ULBP2 (UL16-binding protein 2) is associated with bacterial degradability and phagolysosomal activity. Moreover, S. aureus-induced ULBP2 expression was linked to altered host cell metabolism, including increased cytoplasmic (iso)citrate levels, reduced glycolytic flux, and functional mitochondrial activity. Interestingly, we found that the ability of S. aureus to induce ULBP2 and proinflammatory cytokines in human monocytes depends on a functional ClpP protease in S. aureus These findings indicate that S. aureus activates ULBP2 in human monocytes through immunometabolic mechanisms and reveal that clpP inactivation may function as a potential immune evasion mechanism. Our results provide critical insight into the interplay between the host immune system and S. aureus that has evolved under the dual selective pressure of host immune responses and antibiotic treatment. Our discovery of an immune stimulatory pathway consisting of human monocyte-based defense against S. aureus suggests that targeting the NKG2D pathway holds potential for managing persistent staphylococcal infections.

BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal population of Australia's Northern Territory (NT). However, many people's hepatitis B virus (HBV) status remains unknown. OBJECTIVE: 1. To maximise the utility of existing HBV test and vaccination data in the NT by creating a linked dataset and computerised algorithmic coding. 2. To undertake rigorous quality assurance processes to establish feasibility of using the linked dataset and computerised algorithmic coding for individual care for people living with CHB. METHODS: Step 1: We used deterministic data linkage to merge information from three separate patient databases. HBV testing and vaccination data from 2008-2016 was linked and extracted for 19,314 people from 21 remote Aboriginal communities in the Top End of the NT. Step 2: A computerised algorithm was developed to allocate one of ten HBV codes to each individual. Step 3: A quality assurance process was undertaken by a clinician, using standardised processes, manually reviewing all three databases, for a subset of 5,293 Aboriginal people from five communities to check the accuracy of each allocated code. RESULTS: The process of data linking individuals was highly accurate at 99.9%. The quality assurance process detected an overall error rate of 17.7% on the HBV code generated by the computerised algorithm. Errors occurred in source documentation, primarily from the historical upload of paper-based records to electronic health records. An overall HBV prevalence of 2.6% in five communities was found, which included ten cases of CHB who were previously unaware of infection and not engaged in care. CONCLUSIONS: Data linkage of individuals was highly accurate. Data quality issues and poor sensitivity in the codes produced by the computerised algorithm were uncovered in the quality assurance process. By systematically, manually reviewing all available data we were able to allocate a HBV status to 91% of the study population.

Background: Remote Australian Aboriginal communities have among the highest diagnosed rates of sexually transmissible infections (STIs) in the world. We did a trial to assess whether continuous improvement strategies related to sexual health could reduce infection rates. Methods: In this stepped-wedge, cluster-randomised trial (STIs in remote communities: improved and enhanced primary health care [STRIVE]), we recruited primary health-care centres serving Aboriginal communities in remote areas of Australia. Communities were eligible to participate if they were classified as very remote, had a population predominantly of Aboriginal people, and only had one primary health-care centre serving the population. The health-care centres were grouped into clusters on the basis of geographical proximity to each other, population size, and Aboriginal cultural ties including language connections. Clusters were randomly assigned into three blocks (year 1, year 2, and year 3 clusters) using a computer-generated randomisation algorithm, with minimisation to balance geographical region, population size, and baseline STI testing level. Each year for 3 years, one block of clusters was transitioned into the intervention phase, while those not transitioned continued usual care (control clusters). The intervention phase comprised cycles of reviewing clinical data and modifying systems to support improved STI clinical practice. All investigators and participants were unmasked to the intervention. Primary endpoints were community prevalence and testing coverage in residents aged 16–34 years for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis. We used Poisson regression analyses on the final dataset and compared STI prevalences and testing coverage between control and intervention clusters. All analyses were by intention to treat and models were adjusted for time as an independent covariate in overall analyses. This study was registered with the Australia and New Ze

Background: Young people living in remote Australian Aboriginal communities experience high rates of sexually transmissible infections (STIs). STRIVE (STIs in Remote communities, ImproVed and Enhanced primary care) was a cluster randomised control trial of a sexual health continuous quality improvement (CQI) program. As part of the trial, qualitative research was conducted to explore staff perceptions of the CQI components, their normalisation and integration into routine practice, and the factors which influenced these processes. Methods: In-depth semi-structured interviews were conducted with 41 clinical staff at 22 remote community clinics during 2011-2013. Normalisation process theory was used to frame the analysis of interview data and to provide insights into enablers and barriers to the integration and normalisation of the CQI program and its six specific components. Results: Of the CQI components, participants reported that the clinical data reports had the highest degree of integration and normalisation. Action plan setting, the Systems Assessment Tool, and the STRIVE coordinator role, were perceived as adding value to the program, but were less readily integrated or normalised. The remaining two components (dedicated funding for health promotion and service incentive payments) were seen as least relevant. Our analysis also highlighted factors which enabled greater integration of the CQI components. These included familiarity with CQI tools, increased accountability of health centre staff and the translation of the CQI program into guideline-driven care. The analysis also identified barriers, including high staff turnover, limited time involved in the program and competing clinical demands and programs. Conclusions: Across all of the CQI components, the clinical data reports had the highest degree of integration and normalisation. The action plans, systems assessment tool and the STRIVE coordinator role all complemented the data reports and allowed these co

Background: Young people living in remote Australian Aboriginal communities experience high rates of sexually transmissible infections (STIs). STRIVE (STIs in Remote communities, ImproVed and Enhanced primary care) was a cluster randomised control trial of a sexual health continuous quality improvement (CQI) program. As part of the trial, qualitative research was conducted to explore staff perceptions of the CQI components, their normalisation and integration into routine practice, and the factors which influenced these processes. Methods: In-depth semi-structured interviews were conducted with 41 clinical staff at 22 remote community clinics during 2011-2013. Normalisation process theory was used to frame the analysis of interview data and to provide insights into enablers and barriers to the integration and normalisation of the CQI program and its six specific components. Results: Of the CQI components, participants reported that the clinical data reports had the highest degree of integration and normalisation. Action plan setting, the Systems Assessment Tool, and the STRIVE coordinator role, were perceived as adding value to the program, but were less readily integrated or normalised. The remaining two components (dedicated funding for health promotion and service incentive payments) were seen as least relevant. Our analysis also highlighted factors which enabled greater integration of the CQI components. These included familiarity with CQI tools, increased accountability of health centre staff and the translation of the CQI program into guideline-driven care. The analysis also identified barriers, including high staff turnover, limited time involved in the program and competing clinical demands and programs. Conclusions: Across all of the CQI components, the clinical data reports had the highest degree of integration and normalisation. The action plans, systems assessment tool and the STRIVE coordinator role all complemented the data reports and allowed these co

Background: In high-incidence Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) settings, annual re-testing is an important public health strategy. Using baseline laboratory data (2009–10) from a cluster randomised trial in 67 remote Aboriginal communities, the extent of re-testing was determined, along with the associated patient, staffing and health centre factors. Methods: Annual testing was defined as re-testing in 9–15 months (guideline recommendation) and a broader time period of 5–15 months following an initial negative CT/NG test. Random effects logistic regression was used to determine factors associated with re-testing. Results: Of 10 559 individuals aged ≥16 years with an initial negative CT/NG test (median age = 25 years), 20.3% had a re-test in 9–15 months (23.6% females vs 15.4% males, P < 0.001) and 35.2% in 5–15 months (40.9% females vs 26.5% males, P < 0.001). Factors independently associated with re-testing in 9–15 months in both males and females were: younger age (16–19, 20–24 years); and attending a centre that sees predominantly (>90%) Aboriginal people. Additional factors independently associated with re-testing for females were: being aged 25–29 years, attending a centre that used electronic medical records, and for males, attending a health centre that employed Aboriginal health workers and more male staff. Conclusions: Approximately 20% of people were re-tested within 9–15 months. Re-testing was more common in younger individuals. Findings highlight the importance of recall systems, Aboriginal health workers and male staff to facilitate annual re-testing. Further initiatives may be needed to increase re-testing.

To evaluate a leucocyte esterase test as a predictor of gonorrhoea or chlamydia in asymptomatic Aboriginal males at the Central Australian Aboriginal Congress Male Clinic (Ingkintja), first-void urine samples and clinical information were collected from consecutive asymptomatic males presenting to the Ingkintja in Alice Springs between March 2008 and December 2009. Urine was tested immediately with a leucocyte esterase test dipstick and then by polymerase chain reaction for gonorrhoea and chlamydia. Among the 292 specimens from asymptomatic males, 15.4% were positive for gonorrhoea or chlamydia. In this group, compared with polymerase chain reaction result for gonorrhoea or chlamydia, leucocyte esterase test alone and in combination with age =35 years showed sensitivities of 66.7% and 60%, specificities of 90.7% and 94.7%, positive predictive values of 56.6% and 67.5%, negative predictive values of 93.7% and 92.8% and the area under receiver operating characteristics curve values of 0.79 and 0.85, respectively. Leucocyte esterase tests can reasonably be used as a basis for immediate empirical treatment for gonorrhoea or chlamydia in asymptomatic central Australian Aboriginal men under 35 years of age. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Background: Despite two decades of interventions, rates of sexually transmissible infections (STI) in remote Australian Aboriginal communities remain unacceptably high. Routine notifications data from 2011 indicate rates of chlamydia and gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher respectively than in the non-Indigenous population.Methods/design: STRIVE is a stepped-wedge cluster randomised trial designed to compare a sexual health quality improvement program (SHQIP) to usual STI clinical care delivered in remote primary health care services. The SHQIP is a multifaceted intervention comprising annual assessments of sexual health service delivery, implementation of a sexual health action plan, six-monthly clinical service activity data reports, regular feedback meetings with a regional coordinator, training and financial incentive payments. The trial clusters comprise either a single community or several communities grouped together based on geographic proximity and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea and trichomonas in Aboriginal residents aged 16-34 years, and performance in clinical management of STIs based on best practice indicators. STRIVE will be conducted over five years comprising one and a half years of trial initiation and community consultation, three years of trial conditions, and a half year of data analysis. The trial was initiated in 68 remote Aboriginal health services in the Northern Territory, Queensland and Western Australia.Discussion: STRIVE is the first cluster randomised trial in STI care in remote Aboriginal health services. The trial will provide evidence to inform future culturally appropriate STI clinical care and control strategies in communities with high STI rates.Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044. © 2013 Ward et al.; licensee BioMed Central Ltd.

Background: Despite two decades of interventions, rates of sexually transmissible infections (STI) in remote Australian Aboriginal communities remain unacceptably high. Routine notifications data from 2011 indicate rates of chlamydia and gonorrhoea among Aboriginal people in remote settings were 8 and 61 times higher respectively than in the non-Indigenous population.Methods/design: STRIVE is a stepped-wedge cluster randomised trial designed to compare a sexual health quality improvement program (SHQIP) to usual STI clinical care delivered in remote primary health care services. The SHQIP is a multifaceted intervention comprising annual assessments of sexual health service delivery, implementation of a sexual health action plan, six-monthly clinical service activity data reports, regular feedback meetings with a regional coordinator, training and financial incentive payments. The trial clusters comprise either a single community or several communities grouped together based on geographic proximity and cultural ties. The primary outcomes are: prevalence of chlamydia, gonorrhoea and trichomonas in Aboriginal residents aged 16-34 years, and performance in clinical management of STIs based on best practice indicators. STRIVE will be conducted over five years comprising one and a half years of trial initiation and community consultation, three years of trial conditions, and a half year of data analysis. The trial was initiated in 68 remote Aboriginal health services in the Northern Territory, Queensland and Western Australia.Discussion: STRIVE is the first cluster randomised trial in STI care in remote Aboriginal health services. The trial will provide evidence to inform future culturally appropriate STI clinical care and control strategies in communities with high STI rates.Trial registration: Australian and New Zealand Clinical Trials Registry ACTRN12610000358044. © 2013 Ward et al.; licensee BioMed Central Ltd.

Silicon nanowires are very promising candidates for the sensitive detection of viruses or even early detection of cancer. Due to their small dimensions the attachment of even one particle on their surface leads to detectable changes in their conductivity. In this paper we describe the development (fabrication and testing) of a silicon nanowire biosensor equipped with microfludic channels and automatized data aquisition for the detection of antibodies against a small virus (Aleutian Disease Virus) causing plasmacytosis on mink and ferrets.

The Australian Government's decision to raise taxes on ready-to-drink spirit-based beverages (RTDs; "alcopops") in 2008 caused great controversy. Interest groups have selectively cited evidence to support their points of view. The alcohol industry cited Victorian data from the Australian Secondary Students' Alcohol and Drug Survey (ASSADS) as evidence that the tax had failed, but closer examination of the data suggests that fewer students are drinking, and fewer are drinking at risky or high-risk levels. Excise data from the first full year after the tax came into effect showed a more than 30% reduction in RTD sales and a 1.5% reduction in total pure alcohol sold in Australia. Although understanding the impact of the alcopops tax will require critical analysis of a range of evidence, sales and ASSADS data suggest that the tax has resulted in reduced consumption of RTDs and total alcohol. The most effective and cost-effective measures for reducing consumption and harm are a comprehensive graduated volumetric alcohol taxation system, a minimum price per standard drink, and special measures for particular products that may cause disproportionate harm. While welcoming the alcopops tax, public health advocates have consistently argued for a comprehensive package ofreform that covers pricing, availability and promotion of alcohol, as well as education and treatment services. MJA 2011: 195.

Over 10 % af Europas befolkning lider nu af en eller flere allergiske sygdomme så som høfeber og fødevareallergi. Selv om der i årtier er blevet forsket i det immunologiske respons, som fører til udviklingen af allergiske sygdomme, vides det stadig ikke, hvordan folk udvikler allergi.Hidtil er dendritiske celler blevet betragtet som den gruppe af antigen præsenterende celler, der igangsætter det allergiske respons. Imidlertid har tre artikler, publiceret i Nature i juli 2009, vist at basofile celler i mus kan fungere som antigen præsenterende celler og fremkalde et allergisk Th2 respons hos mus.Formålet med dette speciale var at øge forståelsen for, hvordan et allergisk respons udvikles, ved at undersøge humane basofile cellers evne til at fungere som antigen præsenterende celler, og at sammenligne deres egenskaber til at inducere et proliferativt respons i CD4+ T celler med et respons induceret af en forløber for den dendritiske celle, monocytten. For at kunne studere dette blev forskellige metoder til at oprense basofile celler, CD4+ T celler og monocytter undersøgt, med henblik på etablering af co-kulturer. For at kunne fungere som antigen præsenterende celler skal humane basofile celler besidde bestemte egenskaber. De skal være i stand til at optage og forarbejde antigen, samt kunne præsentere antigen på MHC klasse II molekyler til CD4+ T celler. Derfor omhandlede en del af specialet en undersøgelse af, hvorvidt de human basofile celler besidder de evner, som er nødvendige for at kunne fungere som antigen præsenterende celler.Eksperimenter blev udført in vitro med buffy coats, hvorfra humane perifere blod mononukleære celler blev oprenset for videre at kunne oprense basofile, CD4+ T celler samt monocytter fra disse. Hvorvidt de humane basofile celler fungerede som antigen præsenterende, blev vurderet ud fra deres evne til at inducere et proliferativt respons i CFSE farvede CD4+ T celler ved tilstedeværelse af antigen. Det proliferative respons blev målt vha. flo, More than 10% of the European population is now considered to suffer from at least one type of allergic disease. Even though, the immunological events causing allergic disease have been studied for decades the immunological response behind the development of allergy has still not been unraveled. So far the dendritic cell has been regarded as the antigen presenting cell responsible for initiating the allergic response. However, three articles published in nature in July 2009, showed that the mouse basophil could function as an antigen presenting cell and induce an allergic Th2 response in mice.The aim of this thesis was to increase the understanding of the early development of an allergic reaction, by studying the capacity of the human basophil to function as antigen presenting cells, including comparison of its ability to induce proliferation in CD4+ T cells to that induced by a DC precursor the monocyte. To accomplish this, suitable methods for purifying CD4+ T cells, basophils, and monocytes needed to be studied, so that co-cultures could be established.Furthermore, for the human basophil to function as an antigen presenting cell it needs to posses certain qualities: it must be able to take up antigen, process it, and present it on MHC class II molecules to CD4+ T cells. Hence, the other part of this thesis was to investigate whether human basophils possess some of the abilities essential to an antigen presenting cells.Experiments were performed in vitro using buffy coat derived human peripheral blood mononuclear cells from which basophils, CD4+ T cells, and monocytes were isolated. The function of human basophils as antigen presenting cells was assessed by their ability to induce proliferation of CFSE stained CD4+ T cells in the presence of antigen, and the proliferation was measured by flow cytometry. With the focus on developing a co-culture system that could be used to study the function of human basophils as antigen presenting cells, suitable methods

Objective: To present recent estimates of alcohol consumption and its impact on the health of people in the Northern Territory, and to draw comparisons with Australia as a whole. Design, setting and participants: Descriptive study of alcohol consumption in the NT population, based on sales data and self-report surveys, and alcohol-attributable deaths and hospitalisations among people in the NT in the 2004-05 and 2005-06 financial years using population alcohol-attributable fractions specific to the NT. Main outcome measures: Per capita consumption of pure alcohol, self-reported level of consumption, and age-standardised rates of death and hospitalisation attributable to alcohol.Results: Apparent per capita consumption of pure alcohol for both Aboriginal and non-Aboriginal populations in the NT has been about 14 litres or more per year for many years, about 50% higher than for Australia as a whole. We estimated that there were 120 and 119 alcohol-attributable deaths in the NT in 2004-05 and 2005-06, respectively, at corresponding age-standardised rates of 7.2 and 7.8 per 10000 adult population. Alcohol-attributable deaths occur in the NT at about 3.5 times the rate they do in Australia generally; rates in non-Aboriginal people were about double the national rate, while they were 9-10 times higher in Aboriginal people. There were 2319 and 2544 alcohol-attributable hospitalisations in the NT in 2004-05 and 2005-06, respectively, at corresponding rates of 146.6 and 157.7 per 10000 population (more than twice the national rate). Conclusion: In recent years, alcohol consumption and consequent alcohol-attributable deaths and hospitalisations for both Aboriginal and non-Aboriginal people in the NT have occurred at levels far higher than elsewhere in Australia.