Infectious Diseases - Research Publications
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ItemDetection of HCV-Specific IFN-γ Responses in HCV Antibody and HCV RNA Negative Injecting Drug Users(KOWSAR PUBL, 2014-01)BACKGROUND: Detectable HCV-specific cellular immune responses in HCV antibody and RNA negative people who inject drugs (PWID) raise the question of whether some are resistant to HCV infection. Immune responses from people who have been exposed to hepatitis C virus (HCV) and remain anti-HCV negative are of interest for HCV vaccine development; however, limited research addresses this area. OBJECTIVES: In a cohort of HCV antibody and RNA negative PWID, we assessed whether the presence of HCV-specific IFN-γ responses or genetic associations provide any evidence of protection from HCV infection. PATIENTS AND METHODS: One hundred and ninety-eight participants were examined longitudinally for clinical, behavioral, social, environmental and genetic characteristics (IFNL3 genotype [formally IL-28B] and HLA type). Sixty-one of the 198 participants were HCV antibody and RNA negative, with 53 able to be examined longitudinally for HCV-specific IFN-γ ELISpot T cell responses. RESULTS: Ten of the 53 HCV antibody and RNA negative participants had detectable HCV-specific IFN-γ responses at baseline (18%). The magnitude of IFN-γ responses averaged 131 +/- 96 SFC/106 PBMC and the breadth was mean 1 +/- 1 pool positive. The specificity of responses were mainly directed to E2, NS4b and NS5b. Participants with (10) and without (43) HCV-specific IFN-γ responses did not differ in behavioral, clinical or genetic characteristics (P > 0.05). There was a larger proportion sharing needles (with 70%, without 49%, P = 0.320) and a higher incidence of HCV (with 35.1 per 100 py, 95% CI 14.6, 84.4, without 16.0 per 100 py, 95% CI 7.2, 35.6, P = 0.212) in those with IFN-γ responses, although not statistically significant. Half the participants with baseline IFN-γ responses became HCV RNA positive (5/10), with one of these participants spontaneously clearing HCV. The spontaneous clearer had high magnitude and broad Th1 responses, favorable IFNL3 genotype and favorable HLA types. CONCLUSIONS: This study demonstrated the detection of HCV-specific IFN-γ responses in HCV antibody and RNA negative individuals, with a tendency for HCV-specific IFN-γ responses to be associated with HCV exposure. The potential role of HCV-specific IFN-γ responses in those who remained HCV RNA negative is of value for the development of novel HCV therapeutics.
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ItemHepatitis C Transmission and Treatment in Contact Networks of People Who Inject Drugs(PUBLIC LIBRARY SCIENCE, 2013-11-01)Hepatitis C virus (HCV) chronically infects over 180 million people worldwide, with over 350,000 estimated deaths attributed yearly to HCV-related liver diseases. It disproportionally affects people who inject drugs (PWID). Currently there is no preventative vaccine and interventions feature long treatment durations with severe side-effects. Upcoming treatments will improve this situation, making possible large-scale treatment interventions. How these strategies should target HCV-infected PWID remains an important unanswered question. Previous models of HCV have lacked empirically grounded contact models of PWID. Here we report results on HCV transmission and treatment using simulated contact networks generated from an empirically grounded network model using recently developed statistical approaches in social network analysis. Our HCV transmission model is a detailed, stochastic, individual-based model including spontaneously clearing nodes. On transmission we investigate the role of number of contacts and injecting frequency on time to primary infection and the role of spontaneously clearing nodes on incidence rates. On treatment we investigate the effect of nine network-based treatment strategies on chronic prevalence and incidence rates of primary infection and re-infection. Both numbers of contacts and injecting frequency play key roles in reducing time to primary infection. The change from "less-" to "more-frequent" injector is roughly similar to having one additional network contact. Nodes that spontaneously clear their HCV infection have a local effect on infection risk and the total number of such nodes (but not their locations) has a network wide effect on the incidence of both primary and re-infection with HCV. Re-infection plays a large role in the effectiveness of treatment interventions. Strategies that choose PWID and treat all their contacts (analogous to ring vaccination) are most effective in reducing the incidence rates of re-infection and combined infection. A strategy targeting infected PWID with the most contacts (analogous to targeted vaccination) is the least effective.
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ItemHepatitis C Virus Phylogenetic Clustering Is Associated with the Social-Injecting Network in a Cohort of People Who Inject Drugs(PUBLIC LIBRARY SCIENCE, 2012-10-26)It is hypothesized that social networks facilitate transmission of the hepatitis C virus (HCV). We tested for association between HCV phylogeny and reported injecting relationships using longitudinal data from a social network design study. People who inject drugs were recruited from street drug markets in Melbourne, Australia. Interviews and blood tests took place three monthly (during 2005-2008), with participants asked to nominate up to five injecting partners at each interview. The HCV core region of individual isolates was then sequenced and phylogenetic trees were constructed. Genetic clusters were identified using bootstrapping (cut-off: 70%). An adjusted Jaccard similarity coefficient was used to measure the association between the reported injecting relationships and relationships defined by clustering in the phylogenetic analysis (statistical significance assessed using the quadratic assignment procedure). 402 participants consented to participate; 244 HCV infections were observed in 238 individuals. 26 genetic clusters were identified, with 2-7 infections per cluster. Newly acquired infection (AOR = 2.03, 95% CI: 1.04-3.96, p = 0.037, and HCV genotype 3 (vs. genotype 1, AOR = 2.72, 95% CI: 1.48-4.99) were independent predictors of being in a cluster. 54% of participants whose infections were part of a cluster in the phylogenetic analysis reported injecting with at least one other participant in that cluster during the study. Overall, 16% of participants who were infected at study entry and 40% of participants with newly acquired infections had molecular evidence of related infections with at least one injecting partner. Likely transmission clusters identified in phylogenetic analysis correlated with reported injecting relationships (adjusted Jaccard coefficient: 0.300; p<0.001). This is the first study to show that HCV phylogeny is associated with the injecting network, highlighting the importance of the injecting network in HCV transmission.
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ItemThe Australian national binge drinking campaign: campaign recognition among young people at a music festival who report risky drinking(BMC, 2011-06-20)BACKGROUND: The Australian Government launched a mass media campaign in 2009 to raise awareness of the harms and costs associated risky drinking among young Australians. The aim of this study was to assess if young people attending a music festival who report frequent risky single occasions of drinking (RSOD) recognise the key message of the campaign, "Binge drinking can lead to injuries and regrets", compared to young people who report less frequent RSOD. METHODS: A cross-sectional behavioural survey of young people (aged 16-29 years) attending a music festival in Melbourne, Australia, was conducted in January 2009. We collected basic demographics, information on alcohol and other drug use and sexual health and behaviour during the previous 12 months, and measured recognition of the Australian National Binge Drinking Campaign key message. We calculated the odds of recognition of the key slogan of the Australian National Binge Drinking Campaign among participants who reported frequent RSOD (defined as reported weekly or more frequent RSOD during the previous 12 months) compared to participants who reported less frequent RSOD. RESULTS: Overall, three-quarters (74.7%) of 1072 participants included in this analysis recognised the campaign message. In the adjusted analysis, those reporting frequent RSOD had significantly lower odds of recognising the campaign message compared to those not reporting frequent RSOD (OR 0.7, 95% CI 0.5-0.9), whilst females had significantly greater odds of recognising the campaign message compared to males (OR 1.8, 95% CI 1.4-2.1). CONCLUSIONS: Whilst a high proportion of the target group recognised the campaign, our analysis suggests that participants that reported frequent RSOD - and thus the most important group to target - had statistically significantly lower odds of recognising the campaign message.
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ItemHigh Rates of Hepatitis C Virus Reinfection and Spontaneous Clearance of Reinfection in People Who Inject Drugs: A Prospective Cohort Study(PUBLIC LIBRARY SCIENCE, 2013-11-07)UNLABELLED: Hepatitis C virus reinfection and spontaneous clearance of reinfection were examined in a highly characterised cohort of 188 people who inject drugs over a five-year period. Nine confirmed reinfections and 17 possible reinfections were identified (confirmed reinfections were those genetically distinct from the previous infection and possible reinfections were used to define instances where genetic differences between infections could not be assessed due to lack of availability of hepatitis C virus sequence data). The incidence of confirmed reinfection was 28.8 per 100 person-years (PY), 95%CI: 15.0-55.4; the combined incidence of confirmed and possible reinfection was 24.6 per 100 PY (95%CI: 16.8-36.1). The hazard of hepatitis C reinfection was approximately double that of primary hepatitis C infection; it did not reach statistical significance in confirmed reinfections alone (hazard ratio [HR]: 2.45, 95%CI: 0.87-6.86, p=0.089), but did in confirmed and possible hepatitis C reinfections combined (HR: 1.93, 95%CI: 1.01-3.69, p=0.047) and after adjustment for the number of recent injecting partners and duration of injecting. In multivariable analysis, shorter duration of injection (HR: 0.91; 95%CI: 0.83-0.98; p=0.019) and multiple recent injecting partners (HR: 3.12; 95%CI: 1.08-9.00, p=0.035) were independent predictors of possible and confirmed reinfection. Time to spontaneous clearance was shorter in confirmed reinfection (HR: 5.34, 95%CI: 1.67-17.03, p=0.005) and confirmed and possible reinfection (HR: 3.10, 95%CI: 1.10-8.76, p-value=0.033) than primary infection. Nonetheless, 50% of confirmed reinfections and 41% of confirmed or possible reinfections did not spontaneously clear. CONCLUSIONS: Hepatitis C reinfection and spontaneous clearance of hepatitis C reinfection were observed at high rates, suggesting partial acquired natural immunity to hepatitis C virus. Public health campaigns about the risks of hepatitis C reinfection are required.
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ItemThe use of social networking platforms for sexual health promotion: identifying key strategies for successful user engagement(BMC, 2015-02-06)BACKGROUND: Online social networking platforms such as Facebook and Twitter have grown rapidly in popularity, with opportunities for interaction enhancing their health promotion potential. Such platforms are being used for sexual health promotion but with varying success in reaching and engaging users. We aimed to identify Facebook and Twitter profiles that were able to engage large numbers of users, and to identify strategies used to successfully attract and engage users in sexual health promotion on these platforms. METHODS: We identified active Facebook (n = 60) and Twitter (n = 40) profiles undertaking sexual health promotion through a previous systematic review, and assessed profile activity over a one-month period. Quantitative measures of numbers of friends and followers (reach) and social media interactions were assessed, and composite scores used to give profiles an 'engagement success' ranking. Associations between host activity, reach and interaction metrics were explored. Content of the top ten ranked Facebook and Twitter profiles was analysed using a thematic framework and compared with five poorly performing profiles to identify strategies for successful user engagement. RESULTS: Profiles that were able to successfully engage large numbers of users were more active and had higher levels of interaction per user than lower-ranked profiles. Strategies used by the top ten ranked profiles included: making regular posts/tweets (median 46 posts or 124 tweets/month for top-ranked profiles versus six posts or six tweets for poorly-performing profiles); individualised interaction with users (85% of top-ranked profiles versus 0% for poorly-performing profiles); and encouraging interaction and conversation by posing questions (100% versus 40%). Uploading multimedia material (80% versus 30%) and highlighting celebrity involvement (70% versus 10%) were also key strategies. CONCLUSION: Successful online engagement on social networking platforms can be measured through quantitative (user numbers and interactions) and basic qualitative content analysis. We identified the amount and type of host activity as key strategies for success, and in particular, regular individualised interaction with users, encouraging conversation, uploading multimedia and relevant links, and highlighting celebrity involvement. These findings provide valuable insight for achieving a high level of online engagement through social networking platforms to support successful health promotion initiatives.
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ItemVenue-Based Networks May Underpin HCV Transmissions amongst HIV-Infected Gay and Bisexual Men(PUBLIC LIBRARY SCIENCE, 2016-09-01)BACKGROUND: This study aimed to investigate the potential influence of venue-based networks on HCV transmission in HIV-positive gay and bisexual men (GBM). METHODS: This was a prospectively recruited cohort of HIV-infected GBM with recently-acquired HCV infection resident in Melbourne and Sydney. Clinical and demographic data were collected together with blood samples for HCV sequencing. Phylogenies were inferred and clusters of individuals infected with HCV with genetic sequence homology were identified. Venues used for sourcing sexual partners were identified; sourcing partners from the same venue was considered a potential social link. Using the Jaccard similarity coefficient, associations were identified between the network of sites where men sourced sex partners and transmission relationships as defined by phylogenetic clustering. RESULTS: Forty individuals were recruited, of whom 62.5% were considered to have sexually- and 37.5% IDU-acquired HCV. Venue use was consistent with men being members of a more sexually adventurous gay community subculture. Six phylogenetically-determined pairs or clusters were identified, comprising fifteen (15/28, 53.6%) individuals. Participants belonging to phylogenetic clusters were observed within the same networks. There was a significant correlation between the network and phylogenetic clustering when both cities were considered simultaneously (p = 0.005), raising the possibility that social connections may be important for HCV transmissions. CONCLUSIONS: Venue-based network elicitation is a promising approach for elucidating HCV transmissions amongst HIV-infected GBM. Public health approaches targeting individuals and venues prominent within networks may reduce onward HCV transmission.
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ItemHome-based chlamydia testing of young people attending a music festival--who will pee and post?(Springer Science and Business Media LLC, 2010-06-28)BACKGROUND: Chlamydia is most common among young people, but only a small proportion of Australian young people are tested annually. Home-based chlamydia testing has been piloted in several countries to increase testing rates, but uptake has been low. We aimed to identify predictors of uptake of home-based chlamydia testing to inform future testing programs. METHODS: We offered home-based chlamydia testing kits to participants in a sexual behaviour cross-sectional survey conducted at a music festival in Melbourne, Australia. Those who consented received a testing kit and were asked to return their urine or vaginal swab sample via post. RESULTS: Nine hundred and two sexually active music festival attendees aged 16-29 completed the survey; 313 (35%) opted to receive chlamydia testing kits, and 67 of 313 (21%) returned a specimen for testing. One participant was infected with chlamydia (1% prevalence). Independent predictors of consenting to receive a testing kit included older age, knowing that chlamydia can make women infertile, reporting more than three lifetime sexual partners and inconsistent condom use. Independent predictors of returning a sample to the laboratory included knowing that chlamydia can be asymptomatic, not having had an STI test in the past six months and not living with parents. CONCLUSIONS: A low proportion of participants returned their chlamydia test, suggesting that this model is not ideal for reaching young people. Home-based chlamydia testing is most attractive to those who report engaging in sexual risk behaviours and are aware of the often asymptomatic nature and potential sequelae of chlamydia infection.
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ItemPatterns of Hepatitis C Virus RNA Levels during Acute Infection: The InC3 Study(PUBLIC LIBRARY SCIENCE, 2015-04-02)BACKGROUND: Understanding the patterns of HCV RNA levels during acute hepatitis C virus (HCV) infection provides insights into immunopathogenesis and is important for vaccine design. This study evaluated patterns of HCV RNA levels and associated factors among individuals with acute infection. METHODS: Data were from an international collaboration of nine prospective cohorts of acute HCV (InC3 Study). Participants with well-characterized acute HCV infection (detected within three months post-infection and interval between the peak and subsequent HCV RNA levels ≤ 120 days) were categorised by a priori-defined patterns of HCV RNA levels: i) spontaneous clearance, ii) partial viral control with persistence (≥ 1 log IU/mL decline in HCV RNA levels following peak) and iii) viral plateau with persistence (increase or <1 log IU/mL decline in HCV RNA levels following peak). Factors associated with HCV RNA patterns were assessed using multinomial logistic regression. RESULTS: Among 643 individuals with acute HCV, 162 with well-characterized acute HCV were identified: spontaneous clearance (32%), partial viral control with persistence (27%), and viral plateau with persistence (41%). HCV RNA levels reached a high viraemic phase within two months following infection, with higher levels in the spontaneous clearance and partial viral control groups, compared to the viral plateau group (median: 6.0, 6.2, 5.3 log IU/mL, respectively; P = 0.018). In the two groups with persistence, Interferon lambda 3 (IFNL3) CC genotype was independently associated with partial viral control compared to viral plateau (adjusted odds ratio [AOR]: 2.75; 95%CI: 1.08, 7.02). In the two groups with viral control, female sex was independently associated with spontaneous clearance compared to partial viral control (AOR: 2.86; 95%CI: 1.04, 7.83). CONCLUSIONS: Among individuals with acute HCV, a spectrum of HCV RNA patterns is evident. IFNL3 CC genotype is associated with initial viral control, while female sex is associated with ultimate spontaneous clearance.