An open-label randomised controlled trial evaluating the efficacy of a meningococcal serogroup B (4CMenB) vaccine on Neisseria gonorrhoeae infection in gay and bisexual men: the MenGO study protocol.

BACKGROUND: Gonorrhoea is an ongoing public health concern due to its rising incidence and the emergence of antibiotic resistance. There are an estimated 82 million new Neisseria gonorrhoeae infections each year, with several populations at higher risk for gonococcal infection, including gay and bisexual men (GBM). If left untreated, infection can lead to serious morbidity including infertility, sepsis and increased risk of HIV acquisition. Development of a gonorrhoea vaccine has been challenging, however there is observational evidence that serogroup B meningococcal vaccines, used to protect against the closely related bacteria Neisseria meningitidis, could provide cross-protection against N. gonorrhoeae. METHODS: The MenGO (Meningococcal vaccine efficacy against Gonorrhoea) study is a phase III open-label randomised control trial in GBM to evaluate the efficacy of the four-component meningococcal serogroup B vaccine, 4CMenB, against gonorrhoea. A total of 130 GBM will be recruited at the Gold Coast Sexual Health Clinic, Australia, and randomised to either receive 2 doses of 4CMenB or no intervention. Participants will be followed up for 24 months with testing for N. gonorrhoeae and other sexually transmissible infections every three months. Demographics, sexual behaviour risk, antibiotic use, and blood samples for analysis of N. gonorrhoeae-specific immune responses, will be collected during the study. The primary outcome is the number of N. gonorrhoeae infections in participants over 2 years measured by nucleic acid amplification test (NAAT). Secondary outcomes are vaccine-induced N. gonorrhoeae-specific immune responses, and adverse events in trial participants. DISCUSSION: This trial will determine if the 4CMenB vaccine is able to reduce N. gonorrhoeae infection. If shown to be effective, 4CMenB could be used in gonococcal prevention. Analysis of 4CMenB-induced immune responses will increase understanding of the type of immune response needed to prevent N. gonorrhoeae, which may enable identification of a potential correlate of protection to aid future gonorrhoea vaccine development. TRIAL REGISTRATION: The trial has been registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12619001478101) on 25 October 2019.

Yes to Recreational Drugs and Complementary Medicines But No to Life-Saving Medications: Beliefs Underpinning Treatment Decisions Among PLHIV.

Despite the life-preserving benefits of antiretroviral therapy (ART), some people living with HIV (PLHIV) delay, decline or diverge from recommended treatment while paradoxically being willing to use potentially dangerous substances, such as recreational drugs (RD) and complementary medicines (CM). During 2016 and 2017, interviews were conducted with 40 PLHIV, in Australia to understand drivers underpinning treatment decisions. While many believed ART to be effective, they expressed concerns about long-term effects, frustration over perceived lack of autonomy in treatment decisions and financial, emotional and physical burdens of HIV care. In contrast, they ascribed a sense of self-control over the use of RD and CM, along with multiple professed benefits. The perceived burden of ART emerged as a motivator for deviating from recommended treatment, while positive views towards RD and CM appear to justify use. This study may serve as guidance for the development of future strategies to address barriers to treatment uptake and adherence and subsequently health outcomes for PLHIV in Australia and elsewhere.

Motivations and Barriers to Treatment Uptake and Adherence Among People Living with HIV in Australia: A Mixed-Methods Systematic Review.

In Australia, approximately 30% of people diagnosed with HIV are not accessing treatment and 8% of those receiving treatment fail to achieve viral suppression. Barriers limiting effective care warrant further examination. This mixed-methods systematic review accessed health and social sector research databases between November and December 2015 to identify studies that explored the perspective of people living with HIV in Australia. Articles were included for analysis if they described the experiences, knowledge, attitudes and beliefs, in relation to treatment uptake and adherence, published between January 2000 and December 2015. Quality appraisal utilised the Mixed Methods Appraisal Tool Version 2011. Seventy-two studies that met the inclusion criteria were reviewed. The interplay of lack of knowledge, fear, stigma, physical, emotional and social issues were found to negatively impact treatment uptake and adherence. Strategies targeting both the individual and the wider community are needed to address these barriers.

Loss of prostaglandin D2 synthase: a key molecular event in the transition of a low-grade astrocytoma to an anaplastic astrocytoma.

Reduction in the mRNA and protein expression of lipocalin-like prostaglandin D(2) (PGD(2)) synthase (PGDS), the main arachidonic acid metabolite produced in neurons and glial cells of the central nervous system, is a significant biological event involved in the malignant progression of astrocytomas and is predictive of poor survival. In vitro, the addition of the main PGDS metabolite, PGD(2), to A172 glioblastoma cells devoid of PGDS resulted in antiproliferative activity and cell death. In vitro PGD(2) substitution also enhanced the efficacy of cyclo-oxygenase-2 inhibitors. This finding has exciting implications for early interventional efforts for the grade 2 and 3 astrocytomas.

Resistance to amoebic gill disease (AGD) is characterised by the transcriptional dysregulation of immune and cell cycle pathways.

Amoebic gill disease (AGD) is a parasite-mediated proliferative gill disease capable of affecting a range of teleost hosts. While a moderate heritability for AGD resistance in Atlantic salmon has been reported previously, the mechanisms by which individuals resist the proliferative effects remain poorly understood. To gain more knowledge of this commercially important trait, we compared gill transcriptomes of two groups of Atlantic salmon, one designated putatively resistant, and one designated putatively susceptible to AGD. Utilising a 17k Atlantic salmon cDNA microarray we identified 196 transcripts that were differentially expressed between the two groups. Expression of 11 transcripts were further examined with real-time quantitative RT-PCR (qPCR) in the AGD-resistant and AGD-susceptible animals, as well as non-infected naïve fish. Gene expression determined by qPCR was in strong agreement with the microarray analysis. A large number of differentially expressed genes were involved in immune and cell cycle responses. Resistant individuals displayed significantly higher expression of genes involved in adaptive immunity and negative regulation of the cell cycle. In contrast, AGD-susceptible individuals showed higher expression of acute phase proteins and positive regulators of the cell cycle. Combined with the gill histopathology, our results suggest AGD resistance is acquired rather than innately present, and that this resistance is for the most part associated with the dysregulation of immune and cell cycle pathways.

Transcriptome analyses of amoebic gill disease-affected Atlantic salmon (Salmo salar) tissues reveal localized host gene suppression.

The transcriptome response of Atlantic salmon (Salmo salar) displaying advanced stages of amoebic gill disease (AGD) was investigated. Naïve smolt were challenged with AGD for 19 days, at which time all fish were euthanized and their severity of infection quantified through histopathological scoring. Gene expression profiles were compared between heavily infected and naïve individuals using a 17 K Atlantic salmon cDNA microarray with real-time quantitative RT-PCR (qPCR) verification. Expression profiles were examined in the gill, anterior kidney, and liver. Twenty-seven transcripts were significantly differentially expressed within the gill; 20 of these transcripts were down-regulated in the AGD-affected individuals compared with naïve individuals. In contrast, only nine transcripts were significantly differentially expressed within the anterior kidney and five within the liver. Again the majority of these transcripts were down-regulated within the diseased individuals. A down-regulation of transcripts involved in apoptosis (procathepsin L, cathepsin H precursor, and cystatin B) was observed in AGD-affected Atlantic salmon. Four transcripts encoding genes with antioxidant properties also were down-regulated in AGD-affected gill tissue according to qPCR analysis. The most up-regulated transcript within the gill was an unknown expressed sequence tag (EST) whose expression was 218-fold (+/- SE 66) higher within the AGD affected gill tissue. Our results suggest that Atlantic salmon experiencing advanced stages of AGD demonstrate general down-regulation of gene expression, which is most pronounced within the gill. We propose that this general gene suppression is parasite-mediated, thus allowing the parasite to withstand or ameliorate the host response.

Assessing privacy risks in population health publications using a checklist-based approach.

OBJECTIVE: Recent growth in the number of population health researchers accessing detailed datasets, either on their own computers or through virtual data centers, has the potential to increase privacy risks. In response, a checklist for identifying and reducing privacy risks in population health analysis outputs has been proposed for use by researchers themselves. In this study we explore the usability and reliability of such an approach by investigating whether different users identify the same privacy risks on applying the checklist to a sample of publications. METHODS: The checklist was applied to a sample of 100 academic population health publications distributed among 5 readers. Cohen's κ was used to measure interrater agreement. RESULTS: Of the 566 instances of statistical output types found in the 100 publications, the most frequently occurring were counts, summary statistics, plots, and model outputs. Application of the checklist identified 128 outputs (22.6%) with potential privacy concerns. Most of these were associated with the reporting of small counts. Among these identified outputs, the readers found no substantial actual privacy concerns when context was taken into account. Interrater agreement for identifying potential privacy concerns was generally good. CONCLUSION: This study has demonstrated that a checklist can be a reliable tool to assist researchers with anonymizing analysis outputs in population health research. This further suggests that such an approach may have the potential to be developed into a broadly applicable standard providing consistent confidentiality protection across multiple analyses of the same data.

IQGAP1 and IGFBP2: valuable biomarkers for determining prognosis in glioma patients.

Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.

Chlamydia retesting and retest positivity rates: results from a state-wide laboratory data linkage study in Tasmania, 2012-13.

Background Chlamydia re-infection increases the likelihood of adverse long-term sequelae. Clinical guidelines recommend retesting at 3-12 months for individuals with positive results, to detect re-infections. Retesting and test positivity levels were measured in young people who previously tested positive for chlamydia infection. METHODS: All chlamydia tests conducted during 2012-13 in Tasmanian residents aged 15-29 years were linked. Retesting and retest positivity rates were calculated by sex, age, socioeconomic indicators and test timeframe. RESULTS: Retesting rates were higher in females than males at 3 months (14.5%, n=242/1673 vs 10%, n=71/721) (P<0.01) and 12 months (27%, 265/968 vs 24%, 98/410) (P=0.24). The retesting rate was higher in females living in areas of most disadvantage (35.5%, 154/434) compared with areas of middle and least disadvantage (26% 139/534) (P<0.01). Males were more likely than females to retest positive at 3 months (35%, 25/71 vs 23%, 55/242) (P<0.01); retest positivity at 12 months was 32% in both sexes (males 98/140; females 265/968). Retest positivity was higher in males living in areas of least disadvantage (43%, 3/7) compared with middle (24%, 16/67) (P=0.27) and most (27%, 10/37) (P=0.09); and higher in females living in areas of least disadvantage (39%, 7/18) compared with middle (24%, 29/121) (P<0.01) and most (31%, 48/154) (P=0.02). CONCLUSIONS: Retesting rates are low in Tasmania and retest positivity is high, reinforcing the importance of promoting safer sex practices, partner notification and treatment, and retesting.

Anonymization for outputs of population health and health services research conducted via an online data center.

OBJECTIVE: Online data centers (ODCs) are becoming increasingly popular for making health-related data available for research. Such centers provide good privacy protection during analysis by trusted researchers, but privacy concerns may still remain if the system outputs are not sufficiently anonymized. In this article, we propose a method for anonymizing analysis outputs from ODCs for publication in academic literature. METHODS: We use as a model system the Secure Unified Research Environment, an online computing system that allows researchers to access and analyze linked health-related data for approved studies in Australia. This model system suggests realistic assumptions for an ODC that, together with literature and practice reviews, inform our solution design. RESULTS: We propose a two-step approach to anonymizing analysis outputs from an ODC. A data preparation stage requires data custodians to apply some basic treatments to the dataset before making it available. A subsequent output anonymization stage requires researchers to use a checklist at the point of downloading analysis output. The checklist assists researchers with highlighting potential privacy concerns, then applying appropriate anonymization treatments. CONCLUSION: The checklist can be used more broadly in health care research, not just in ODCs. Ease of online publication as well as encouragement from journals to submit supplementary material are likely to increase both the volume and detail of analysis results publicly available, which in turn will increase the need for approaches such as the one suggested in this paper.

Exploration of testing practices and population characteristics support an increase in chlamydia positivity in Tasmania between 2001 and 2010.

OBJECTIVE: The proportion of positive chlamydia tests in young people in Tasmania increased significantly between 2001 and 2010. While female positivity rates increased steadily, male positivity rose steeply to 2005 then stabilised. Crude positivity rates can be influenced by a variety of factors making interpretation difficult. Unique Tasmanian datasets were used to explore whether symptom status, reason for testing or sexual exposure could explain the observed positivity trends. METHODS: Population-level chlamydia positivity rates in Tasmania over a 10-year period were compared with surveillance data collected on people aged 15 to 29 years notified with chlamydia. RESULTS: The proportion of asymptomatic chlamydia cases increased, with the largest increase in males aged 15 to 19 years (28%). Opportunistic testing of cases increased (greatest in males, range 17-32%). Sexual exposure remained consistent. CONCLUSIONS: After allowing for any changes in sexual exposure, symptom status and reason for testing, an increase in chlamydia positivity occurred over the 10 years. Healthcare providers have increased chlamydia testing in high-risk groups. IMPLICATIONS: Monitoring chlamydia testing patterns and positivity rates at a population level is a step forward in surveillance practices. Targeted surveys provide valuable information to supplement routine surveillance data.

Improving public health surveillance of chlamydia: analysis of population-level positivity trends.

UNLABELLED: Background Chlamydia remains Australia's most frequently notified communicable disease; however, interpretation of notification data is difficult without knowledge of testing practices. This study examined the value of reporting positivity trends. METHODS: Tasmanian population-level chlamydia laboratory tests and notification data from 2001 to 2010 were compared. RESULTS: Notifications, tests and positivity increased, most significantly in males and females aged 15-29 years. CONCLUSIONS: Analysis of chlamydia positivity trends can inform the development, monitoring and evaluation of prevention and control activities and improves the interpretation of notification trends. After allowing for testing effort, an increase in chlamydia infections in young people was found.

Tris lipidation--a novel drug delivery system that alters biodistribution.

Tris-lipidation uses Tris to produce drug-fatty acyl conjugates. Radiolabelled Tris-fatty acyl conjugates of methotrexate (MTX) were examined in biodistribution studies in BALB/c mice. Following delivery via a variety of routes, the Tris-lipidated compounds demonstrated features in common with other colloid drug delivery systems. Tissues of the reticuloendothelial system localised the drug following intravenous administration, and the compounds showed prolongation at the site of injection into muscle or fatty tissue, subcutaneously or when inhaled. These findings indicate that the Tris-lipidation platform could be classed as an alternative colloid drug delivery system.

Public health policies and management strategies for genital Chlamydia trachomatis infection.

Genital Chlamydia trachomatis is a sexually transmissible bacterial infection that is asymptomatic in the majority of infected individuals and is associated with significant short-term and long-term morbidity. The population prevalence of the infection appears to be increasing. C. trachomatis is of public health significance because of the impacts of untreated disease on reproductive outcomes, transmission of other sexually acquired infections, and the costs to health systems. At the individual level, C. trachomatis infection is readily treatable with antibiotics, although antibiotic resistance appears to be increasing. At the population level, public health control of spread of infection is more problematic. Approaches to control include primary preventive activities, increased access to testing and treatment for people with or at risk of infection, partner notification and treatment, and screening either opportunistically or as part of an organized population screening program. A combination of all of the above approaches is likely to be required to have a significant effect on the burden of disease associated with genital chlamdyia infection and to reduce population prevalence. The development of a vaccine for genital chlamydia infection could significantly reduce the public health burden associated with infection; however a vaccine is not expected to be available in the near future.

Chlamydia trachomatis in Tasmania 2001-2007: rising notification trends.

OBJECTIVES: To investigate trends in notification rates of Chlamydia trachomatis in Tasmania, Australia, by population sub-groups, from 1 January 2001 to 31 December 2007. METHODS: An enhanced surveillance dataset was used to supplement case notifications. Rates based on age group were analysed by sex, geographic region, indigenous status, sexual exposure, reason for testing and healthcare provider. RESULTS: In all age groups, the notification rate increased steeply. The highest rates were seen in the ages 15-24 years; this age group represented 15% of the population but accounted for 74% of the chlamydial notifications. The increased rates in females aged 15-24 years and males 15-19 years in Tasmania were larger than the increases observed nationally. Rates were consistently higher in urban areas. Females were more likely to have been tested as a result of screening, and males were more likely to have been tested when presenting with symptoms or as a result of contact tracing. The majority of cases reported sexual exposure with opposite sex partners only. CONCLUSIONS: This study highlights the increasing significance of chlamydial infection as a public health issue, the gender differences in health-seeking behaviour, and the discrepancies in testing patterns. These findings will assist with the design of health promotion programs.

Role of the general practitioner in testing for genital Chlamydia trachomatis infection: an analysis of enhanced surveillance data.

BACKGROUND: To examine the relationship between genital chlamydia testing by healthcare providers and patient demographic characteristics in Tasmania, Australia, from 2001 to 2007. METHODS: Analysis of enhanced surveillance data for genital Chlamydia trachomatis infections notified to the Tasmanian Communicable Diseases Prevention Unit between 1 January 2001 and 31 December 2007. RESULTS: General practitioners identify most cases of genital chlamydia infection, irrespective of patient age, gender, indigenous status or urban status. Tests that are performed for screening purposes identify the largest number of cases in females, particularly in very young females. In males, tests performed due to the presence of clinical symptoms identify the majority of cases. However, tests performed for the purposes of contact tracing also identify a substantial burden of genital chlamydia infection, particularly in males. CONCLUSIONS: The present study demonstrates the critical role the general practitioner has in the identification of genital chlamydia infection. Opportunistic screening for genital chlamydia, including in the context of contact tracing, is an essential clinical activity that results in the identification of substantial numbers of cases of infection. Policy makers and public health practitioners should support general practice screening initiatives and remove the barriers to genital chlamydia screening in general practice.

Study of knowledge of genital herpes infection and attitudes to testing for genital herpes among antenatal clinic attendees.

A descriptive survey of knowledge of genital herpes and attitudes to testing was conducted among antenatal clinic attendees at the Gold Coast Hospital, Australia. The study subjects showed a good knowledge of genital herpes, to a level that appears sufficient for an informed choice regarding herpes serology testing to be made. A preference for testing for genital herpes was suggested. Although serological testing is not routinely required, the results of the study indicate that discussion of genital herpes should be considered in the antenatal clinic setting.