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1.  Do Australian general practitioners believe practice nurses can take a role in chlamydia testing? A qualitative study of attitudes and opinions 
Background
Chlamydia notifications continue to rise in young people in many countries and regular chlamydia testing is an important prevention strategy. Although there have been initiatives to increase testing in primary care, none have specifically investigated the role of practice nurses (PNs) in maximising testing rates. PNs have previously expressed a willingness to be involved, but noted lack of support from general practitioners (GPs) as a barrier. We sought GPs’ attitudes and opinions on PNs taking an expanded role in chlamydia testing and partner notification.
Methods
In the context of a cluster randomised trial in mostly rural towns in 4 Australian states, semi structured interviews were conducted with 44 GPs between March 2011 and July 2012. Data relating to PN involvement in chlamydia testing were thematically analysed using a conventional content analysis approach.
Results
The majority of GPs interviewed felt that a role for PNs in chlamydia testing was appropriate. GPs felt that PNs had more time for patient education and advice, that patients would find PNs easier to talk to and less intimidating than GPs, and that GPs themselves could benefit through a reduction in their workload. Although GPs felt that PNs could be utilised more effectively for preventative health activities such as chlamydia testing, many raised concerns about how these activities would be renumerated whilst some felt that existing workload pressures for PNs could make it difficult for them to expand their role. Whilst some rural GPs recognised that PNs might be well placed to conduct partner notification, they also recognised that issues of patient privacy and confidentiality related to living in a “small town” was also a concern.
Conclusion
This is the first qualitative study to explore GPs’ views around an increased role for PNs in chlamydia testing. Despite the concerns raised by PNs, these findings suggest that GPs support the concept and recognise that PNs are suited to the role. However issues raised, such as funding and remuneration may act as barriers that will need to be addressed before PNs are supported to make a contribution to increasing chlamydia testing rates in general practice.
doi:10.1186/s12879-015-0757-7
PMCID: PMC4314754
2.  Early IL-10 predominant responses are associated with progression to chronic hepatitis C virus infection in injecting drug users 
Journal of viral hepatitis  2010;18(8):549-561.
Background
The critical events in clearance or persistence of hepatitis C virus (HCV) infection are unknown, but likely to be determined early in acute infection.
Methods
Type 1 and type 2 cytokine production was assessed by HCV peptide ELISpot and multiplex in vitro cytokine production assays in longitudinally collected samples from 20 untreated participants enrolled in the Australian Trial in Acute Hepatitis C (ATAHC); a prospective cohort of acute HCV infection (77% injecting drug users, IDU).
Results
Significantly higher interleukin-10 (IL-10) production (p=0.048), in the relative absence of interferon-gamma (IFN-γ) and IL-2 production, was present early in HCV infection in those who progressed to chronic infection. In contrast, viral clearance was associated with a greater magnitude and broader specificity of IFN-γ (magnitude p<0.001, breadth p=0.004) and IL-2 responses, in the relative absence of IL-10. Early IL-10 production was correlated with higher HCV RNA level at baseline (p=0.046) and week 12 (p=0.018), while IFN-γ and IL-2 production was inversely correlated with HCV RNA level at baseline (IFN-γ p=0.020, IL-2 p=0.050) and week 48 (IFN-γ p=0.045, IL-2 p=0.026). Intracellular staining (ICS) indicated the HCV-specific IFN-γ response was primarily from CD8+ T cells and NK cells, whereas IL-10 production was predominantly from monocytes, with a subset of IL-10 producing CD8+ T cells present only in those who progressed to chronic infection.
Conclusion
IL-10, an immunoregulatory cytokine, appears to play a key role in progression to chronic HCV infection.
doi:10.1111/j.1365-2893.2010.01335.x
PMCID: PMC4277610  PMID: 20626625
cytokine balance; cellular immunity; HCV infection; injection drug use; IL-10
3.  Dynamics of HCV RNA levels during acute hepatitis C virus infection 
Journal of medical virology  2014;86(10):1722-1729.
Understanding viral dynamics during acute hepatitis C virus (HCV) infection can provide important insights into immunopathogenesis and guide early treatment. The aim of this study was investigating the dynamics of HCV RNA and alanine transaminase (ALT) levels during recent HCV infection in the Australian Trial in Acute Hepatitis C (ATAHC). ATAHC was a prospective study of the natural history of recently acquired HCV infection. Longitudinal HCV RNA and ALT levels were compared among individuals with ultimately persistent infection and spontaneous clearance outcomes. Among those with HCV persistence (n=104) and HCV clearance (n=30), median HCV RNA (5.2 vs. 4.1 log IU/mL, respectively) and ALT levels (779 vs. 1765 IU/L, respectively) were high during month two following infection, and then declined during months three and four in both groups. Among those with HCV persistence, median HCV RNA was 2.9 log IU/mL during months four, increased to 5.5 log IU/mL during month five, and remained subsequently relatively stable. Among those with HCV clearance, median HCV RNA was undetectable by month five. Median HCV RNA levels were comparable between individuals with HCV persistence and HCV clearance during month three following infection (3.2 vs. 3.5 log IU/mL, respectively; P=0.935), but markedly different during month five (5.5 vs. 1.0 log IU/mL, respectively; P<0.001). In conclusion, dynamics of HCV RNA levels in those with HCV clearance and HCV persistence diverged between months three and five following infection, with the latter time-point being potentially useful for commencing early treatment.
doi:10.1002/jmv.24010
PMCID: PMC4276420  PMID: 25042465
Chronic; Persistent infection; Spontaneous clearance; Viral load; alanine transaminase
5.  Improving chlamydia knowledge should lead to increased chlamydia testing among Australian general practitioners: a cross-sectional study of chlamydia testing uptake in general practice 
BMC Infectious Diseases  2014;14(1):584.
Background
Female general practitioners (GPs) have higher chlamydia testing rates than male GPs, yet it is unclear whether this is due to lack of knowledge among male GPs or because female GPs consult and test more female patients.
Methods
GPs completed a survey about their demographic details and knowledge about genital chlamydia. Chlamydia testing and consultation data for patients aged 16-29 years were extracted from the medical records software for each GP and linked to their survey responses. Chi-square tests were used to determine differences in a GP’s knowledge and demographics. Two multivariable models that adjusted for the gender of the patient were used to investigate associations between a GP and their chlamydia testing rates ― Model 1 included GPs’ characteristics such as age and gender, Model 2 excluded these characteristics to specifically examine any associations with knowledge.
Results
Female GPs were more likely than male GPs to know when to re-test a patient after a negative chlamydia test (18.8% versus 9.7%, p = 0.01), the correct symptoms suggestive of PID (80.5% versus 67.8%, p = 0.01) and the correct tests for diagnosing PID (57.1% versus 42.6%, p = 0.01). Female GPs tested 6.5% of patients, while male GPs tested 2.2% (p < 0.01). Model 1 found factors associated with chlamydia testing were being a female GP (OR = 2.5, 95% CI: 1.9, 3.3) and working in a metropolitan clinic (OR = 3.2; 95% CI: 2.4, 4.3). Model 2 showed that chlamydia testing increased as knowledge of testing guidelines improved (3-5 correct answers – AOR = 2.0, 95% CI: 1.0, 4.2; 6+ correct answers – AOR = 2.9, 95% CI: 1.4, 6.2).
Conclusions
Higher rates of chlamydia testing are strongly associated with GPs who are female, based in a metropolitan clinic and among those with more knowledge of the recommended guidelines. Improving chlamydia knowledge among male GPs may increase chlamydia testing.
doi:10.1186/s12879-014-0584-2
PMCID: PMC4228271  PMID: 25409698
Chlamydia testing; General practice; Sexual health knowledge; General practitioner education
6.  Maintenance of Th1 HCV-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment 
Journal of gastroenterology and hepatology  2013;28(11):10.1111/jgh.12265.
Background and aim
T cell responses against hepatitis C are believed to be critical in achieving both natural and treatment induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 HCV-specific cytokine production and T cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C (ATAHC) comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance.
Methods
HCV-specific T cell responses were characterised by HCV peptide ELISpot, in-vitro cytokine production and T cell flow cytometry assays.
Results
Treated subjects with a SVR displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon (IFN)-γ and interleukin (IL)-2 magnitude week 24, broader IFN-γ responses week 24 and 48, p<0.05), and significantly increased IFN-γ responses between screening and week 48 (magnitude p=0.026, breadth p=0.009). Treatment-induced viral clearance was also associated with a trend towards decreased IL-10 responses (screening to week 48 p=0.070), higher expression of CD45RO (p=0.042) and CD38 (p=0.088) on CD4+ T cells and higher IFN-γR expression (CD56+IFN-γR+ p=0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection, however IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth p=0.064).
Conclusion
Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses.
doi:10.1111/jgh.12265
PMCID: PMC3808486  PMID: 23663030
Acute hepatitis C; injecting drug users; immune response; PEG-IFN-α; T cells
7.  How Are Health Research Priorities Set in Low and Middle Income Countries? A Systematic Review of Published Reports 
PLoS ONE  2014;9(10):e108787.
Background
Priority setting is increasingly recognised as essential for directing finite resources to support research that maximizes public health benefits and drives health equity. Priority setting processes have been undertaken in a number of low- and middle-income country (LMIC) settings, using a variety of methods. We undertook a critical review of reports of these processes.
Methods and Findings
We searched electronic databases and online for peer reviewed and non-peer reviewed literature. We found 91 initiatives that met inclusion criteria. The majority took place at the global level (46%). For regional or national initiatives, most focused on Sub Saharan Africa (49%), followed by East Asia and Pacific (20%) and Latin America and the Caribbean (18%). A quarter of initiatives aimed to cover all areas of health research, with a further 20% covering communicable diseases. The most frequently used process was a conference or workshop to determine priorities (24%), followed by the Child Health and Nutrition Initiative (CHNRI) method (18%). The majority were initiated by an international organization or collaboration (46%). Researchers and government were the most frequently represented stakeholders. There was limited evidence of any implementation or follow-up strategies. Challenges in priority setting included engagement with stakeholders, data availability, and capacity constraints.
Conclusions
Health research priority setting (HRPS) has been undertaken in a variety of LMIC settings. While not consistently used, the application of established methods provides a means of identifying health research priorities in a repeatable and transparent manner. In the absence of published information on implementation or evaluation, it is not possible to assess what the impact and effectiveness of health research priority setting may have been.
doi:10.1371/journal.pone.0108787
PMCID: PMC4183511  PMID: 25275315
8.  Impact of Male Circumcision on the HIV Epidemic in Papua New Guinea: A Country with Extensive Foreskin Cutting Practices 
PLoS ONE  2014;9(8):e104531.
The degree to which adult medical male circumcision (MC) programs can reduce new HIV infections in a moderate HIV prevalence country like Papua New Guinea (PNG) are uncertain especially given the widespread prevalence of longitudinal foreskin cuts among adult males. We estimated the likely impact of a medical MC intervention in PNG using a mathematical model of HIV transmission. The model was age-structured and incorporated separate components for sex, rural/urban, men who have sex with men and female sex workers. Country-specific data of the prevalence of foreskin cuts, sexually transmitted infections, condom usage, and the acceptability of MC were obtained by our group through related studies. If longitudinal foreskin cutting has a protective efficacy of 20% compared to 60% for MC, then providing MC to 20% of uncut males from 2012 would require 376,000 procedures, avert 7,900 HIV infections by 2032, and require 143 MC per averted infection. Targeting uncut urban youths would achieve the most cost effective returns of 54 MC per HIV infection averted. These numbers of MC required to avert an HIV infection change little even with coverage up to 80% of men. The greater the protective efficacy of longitudinal foreskin cuts against HIV acquisition, the less impact MC interventions will have. Dependent on this efficacy, increasing condom use could have a much greater impact with a 10 percentage point increase averting 18,400 infections over this same period. MC programs could be effective in reducing HIV infections in PNG, particularly in high prevalence populations. However the overall impact is highly dependent on the protective efficacy of existing longitudinal foreskin cutting in preventing HIV.
doi:10.1371/journal.pone.0104531
PMCID: PMC4128698  PMID: 25111058
9.  Chlamydia among Australian Aboriginal and/or Torres Strait Islander people attending sexual health services, general practices and Aboriginal community controlled health services 
Background
Chlamydia infections are notified at much higher rates in Aboriginal and/or Torres Strait Islander people compared to non-Indigenous people. The Australian Collaboration Chlamydia Enhanced Sentinel Surveillance System (ACCESS) was established to complement population-based surveillance.
Methods
We describe patient demographics, completeness of recording of Aboriginal and/or Torres Strait Islander (‘Aboriginal’) status, chlamydia testing rates and positivity rates from the Aboriginal Community Controlled Health Service (ACCHSs), General Practice (GP) clinics and Sexual Health Services (SHSs) networks in ACCESS during 2009. Data were extracted from electronic medical records of each participating health service for consultations with patients aged 16–29 years and for chlamydia testing and positivity.
Results
Data were included from 16–29 year olds attending six ACCHSs (n = 4,950); 22 SHSs (n = 20,691) and 25 GP clinics (n = 34,462). Aboriginal status was unknown for 79.3% of patients attending GP clinics, 4.5% attending SHSs and 3.8% of patients attending ACCHSs. Chlamydia testing rates among Aboriginal patients were 19.8% (95%CI:18.6%-21.0%) at ACCHSs, 75.5% (95% CI:72.5%-78.4%) at SHSs and 4.3% (95% CI: 2.6%-6.6%) at GP clinics. Positivity rates were highest in Aboriginal patients tested at SHSs at 22.7% (95% CI:19.5%-26.2%), followed by 15.8% (95% CI:3.8%-43.4%) at GP clinics and 8.6% at ACCHSs (95% CI:7.9%-12.4%). This compared with non-Indigenous patients positivity rates at SHSs of 12.7% (95% CI:12.2-13.2%); 8.6% (7.2%-11.3%) at GP clinics and 11.3% at ACCHSs (95% CI:15.4%-24.9%).
Conclusions
Higher chlamydia positivity in Aboriginal people across a range of clinical services is reflected in national notification data. Targeted efforts are required to improve testing rates in primary care services; to improve identification of Aboriginal patients in mainstream services such as GP clinics; and to better engage with young Aboriginal Australians.
doi:10.1186/1472-6963-14-285
PMCID: PMC4094446  PMID: 24981418
Chlamydia; Aboriginal and Torres Strait Islander people; Testing; Positivity; Indigenous; Australia
10.  Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection 
Hepatology (Baltimore, Md.)  2013;57(6):2124-2134.
Systemic levels of interferon-gamma-inducible protein-10 (IP-10) are predictive of treatment-induced clearance in chronic HCV. In the present study, factors associated with plasma IP-10 levels at the time of acute HCV detection and the association between IP-10 levels and spontaneous clearance were assessed in three cohorts of acute HCV infection. Among 300 individuals, 245 (181 male, 47 HIV+) were HCV RNA+ at acute HCV detection. In adjusted analysis, factors independently associated with IP-10 levels ≥150 pg/mL (median level) included HCV RNA levels >6 log IU/mL, HIV co-infection and non-Aboriginal ethnicity. Among 245 HCV RNA+ at acute HCV detection, 214 were untreated (n=137) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=77). Spontaneous clearance occurred in 14% (29 of 214). Individuals without spontaneous clearance had significantly higher mean plasma IP-10 levels at the time of acute HCV detection than those with clearance (248±32 vs. 142±22 pg/mL, P=0.008). The proportion of individuals with spontaneous clearance was 0% (0 of 22, P=0.048) and 16% (27 of 165) and in those in those with and without plasma IP-10 levels ≥380 pg/mL. In adjusted analyses, favourable IL28B genotype was associated with spontaneous clearance, while higher HCV RNA level was independently associated with lower odds of spontaneous clearance.
Conclusion
High IP-10 levels at acute HCV detection were associated with failure to spontaneously clear HCV. Patients with acute HCV and high baseline IP-10 levels, particularly >380 pg/mL, should be considered for early therapeutic intervention, and those with low levels should defer therapy for potential spontaneous clearance.
doi:10.1002/hep.26263
PMCID: PMC3663887  PMID: 23325615
IP-10; CXCL10; spontaneous clearance; acute; HCV RNA; HIV
12.  Rationale and design of REACT: a randomised controlled trial assessing the effectiveness of home-collection to increase chlamydia retesting and detect repeat positive tests 
BMC Infectious Diseases  2014;14:223.
Background
Repeat infection with Chlamydia trachomatis is common and increases the risk of sequelae in women and HIV seroconversion in men who have sex with men (MSM). Despite guidelines recommending chlamydia retesting three months after treatment, retesting rates are low. We are conducting the first randomised controlled trial to assess the effectiveness of home collection combined with short message service (SMS) reminders on chlamydia retesting and reinfection rates in three risk groups.
Methods/Design
The REACT (retest after Chlamydia trachomatis) trial involves 600 patients diagnosed with chlamydia: 200 MSM, 200 women and 200 heterosexual men recruited from two Australian sexual health clinics where SMS reminders for retesting are routine practice. Participants will be randomised to the home group (3-month SMS reminder and home-collection) or the clinic group (3-month SMS reminder to return to the clinic). Participants in the home group will be given the choice of attending the clinic if they prefer. The mailed home-collection kit includes a self-collected vaginal swab (women), UriSWAB (Copan) for urine collection (heterosexual men), and UriSWAB plus rectal swab (MSM). The primary outcome is the retest rate at 1-4 months after a chlamydia diagnosis, and the secondary outcomes are: the repeat positive test rate; the reinfection rate; the acceptability of home testing with SMS reminders; and the cost effectiveness of home testing. Sexual behaviour data collected via an online survey at 4-5 months, and genotyping of repeat infections, will be used to discriminate reinfections from treatment failures. The trial will be conducted over two years. An intention to treat analysis will be conducted.
Discussion
This study will provide evidence about the effectiveness of home-collection combined with SMS reminders on chlamydia retesting, repeat infection and reinfection rates in three risk groups. The trial will determine client acceptability and cost effectiveness of this strategy.
Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN12611000968976.
doi:10.1186/1471-2334-14-223
PMCID: PMC4002559  PMID: 24758169
Chlamydia; Retesting; Positivity; Reinfection; Home-collection
13.  Hospitalisations for Pelvic Inflammatory Disease Temporally Related to a Diagnosis of Chlamydia or Gonorrhoea: A Retrospective Cohort Study 
PLoS ONE  2014;9(4):e94361.
Objectives
The presence and severity of pelvic inflammatory disease (PID) symptoms are thought to vary by microbiological etiology but there is limited empirical evidence. We sought to estimate and compare the rates of hospitalisation for PID temporally related to diagnoses of gonorrhoea and chlamydia.
Methods
All women, aged 15–45 years in the Australian state of New South Wales (NSW), with a diagnosis of chlamydia or gonorrhoea between 01/07/2000 and 31/12/2008 were followed by record linkage for up to one year after their chlamydia or gonorrhoea diagnosis for hospitalisations for PID. Standardised incidence ratios compared the incidence of PID hospitalisations to the age-equivalent NSW population.
Results
A total of 38,193 women had a chlamydia diagnosis, of which 483 were hospitalised for PID; incidence rate (IR) 13.9 per 1000 person-years of follow-up (PYFU) (95%CI 12.6–15.1). In contrast, 1015 had a gonorrhoea diagnosis, of which 45 were hospitalised for PID (IR 50.8 per 1000 PYFU, 95%CI 36.0–65.6). The annual incidence of PID hospitalisation temporally related to a chlamydia or gonorrhoea diagnosis was 27.0 (95%CI 24.4–29.8) and 96.6 (95%CI 64.7–138.8) times greater, respectively, than the age-equivalent NSW female population. Younger age, socio-economic disadvantage, having a diagnosis prior to 2005 and having a prior birth were also associated with being hospitalised for PID.
Conclusions
Chlamydia and gonorrhoea are both associated with large increases in the risk of PID hospitalisation. Our data suggest the risk of PID hospitalisation is much higher for gonorrhoea than chlamydia; however, further research is needed to confirm this finding.
doi:10.1371/journal.pone.0094361
PMCID: PMC3990571  PMID: 24743388
14.  How Effective Are Short Message Service Reminders at Increasing Clinic Attendance? A Meta-Analysis and Systematic Review 
Health Services Research  2011;47(2):614-632.
Background and Objectives
In the last few years there has been a steady uptake of mobile phone short message service (SMS) reminders to increase medical attendance rates. We undertook a review of studies that assessed the effectiveness of SMS reminders at increasing the uptake of appointments in health care settings.
Methods
We reviewed studies which involved a comparison of appointment attendance rates between patients who did and did not receive SMS reminders published prior to June 2010. We used meta-analysis methods to calculate the overall effect on attendance rates, stratified by study design and clinic type.
Results
The review criteria were met by 18 reports, made up of eight randomized controlled trials (RCTs) and 10 controlled observational studies. Across all studies, there was significant heterogeneity in the estimated effect measure of the relationship between use of SMS reminders and clinic attendance (I2 = 90 percent; p < .01), so a summary effect estimate was not calculated. Stratification by study design showed that the heterogeneity was due to the observational studies. The summary effect from the RCTs was 1.48 (95% CI: 1.23–1.72) with no significant subgroup differences by clinic type (primary care clinics, hospital outpatient clinics), message timing (24, 48, and 72+ hours before the scheduled appointment), and target age group (pediatric, older).
Conclusions
Short message service reminders in health care settings substantially increase the likelihood of attending clinic appointments. SMS reminders appear to be a simple and efficient option for health services to use to improve service delivery, as well as resulting in health benefits for the patients who receive the reminders.
doi:10.1111/j.1475-6773.2011.01342.x
PMCID: PMC3419880  PMID: 22091980
Reminder systems; appointment; health services; review
15.  A Laboratory-Based Evaluation of Four Rapid Point-of-Care Tests for Syphilis 
PLoS ONE  2014;9(3):e91504.
Background
Syphilis point-of-care tests may reduce morbidity and ongoing transmission by increasing the proportion of people rapidly treated. Syphilis stage and co-infection with HIV may influence test performance. We evaluated four commercially available syphilis point-of-care devices in a head-to-head comparison using sera from laboratories in Australia.
Methods
Point-of-care tests were evaluated using sera stored at Sydney and Melbourne laboratories. Sensitivity and specificity were calculated by standard methods, comparing point-of-care results to treponemal immunoassay (IA) reference test results. Additional analyses by clinical syphilis stage, HIV status, and non-treponemal antibody titre were performed. Non-overlapping 95% confidence intervals (CI) were considered statistically significant differences in estimates.
Results
In total 1203 specimens were tested (736 IA-reactive, 467 IA-nonreactive). Point-of-care test sensitivities were: Determine 97.3%(95%CI:95.8–98.3), Onsite 92.5%(90.3–94.3), DPP 89.8%(87.3–91.9) and Bioline 87.8%(85.1–90.0). Specificities were: Determine 96.4%(94.1–97.8), Onsite 92.5%(90.3–94.3), DPP 98.3%(96.5–99.2), and Bioline 98.5%(96.8–99.3). Sensitivity of the Determine test was 100% for primary and 100% for secondary syphilis. The three other tests had reduced sensitivity among primary (80.4–90.2%) compared to secondary syphilis (94.3–98.6%). No significant differences in sensitivity were observed by HIV status. Test sensitivities were significantly higher among high-RPR titre (RPR≥8) (range: 94.6–99.5%) than RPR non-reactive infections (range: 76.3–92.9%).
Conclusions
The Determine test had the highest sensitivity overall. All tests were most sensitive among high-RPR titre infections. Point-of-care tests have a role in syphilis control programs however in developed countries with established laboratory infrastructures, the lower sensitivities of some tests observed in primary syphilis suggest these would need to be supplemented with additional tests among populations where syphilis incidence is high to avoid missing early syphilis cases.
doi:10.1371/journal.pone.0091504
PMCID: PMC3950184  PMID: 24618681
16.  Male Circumcision and HIV Transmission; What Do We Know? 
The Open AIDS Journal  2014;8:31-44.
Male circumcision (MC) has been shown to be protective against heterosexual HIV transmission and is being explored in some parts of the world as a means of combating the epidemic. The World Health Organization (WHO) recommends that MC be considered as an important component of HIV prevention in high prevalence settings.
We review evidence that demonstrates that the inner foreskin is likely to be the main portal of entry for the HIV virus in males. Whether removal of the inner foreskin accounts for all the protection afforded by circumcision is yet to be established.
The proposed mechanisms of protection range from inherent immunohistological factors of foreskin such as difference in thickness of keratin layer and density of target cells for HIV between inner and outer foreskin to physiological mechanisms that follow male circumcision such as drying of secretions underneath foreskin after sexual intercourse, loss of microbiome that attract target cells to the genital mucosa and lack of priming the genital mucosa with less abundant sexual transmitted infections among circumcised men.
The aim of this review is to give an updated account on the mechanisms proposed so far on the demonstrated 50-70% protection from HIV transmission through heterosexual intercourse, by male circumcision.
doi:10.2174/1874613601408010031
PMCID: PMC4192839  PMID: 25317221
Circumcision; foreskin; HIV transmission; immune cells; keratin layer.
17.  Plasma Interferon-Gamma-Inducible Protein-10 Levels Are Associated with Early, but Not Sustained Virological Response during Treatment of Acute or Early Chronic HCV Infection 
PLoS ONE  2013;8(11):e80003.
Background
High plasma levels of interferon-gamma inducible protein-10 (IP-10) have been shown to be associated with impaired treatment response in chronic hepatitis C virus (HCV) infection. Whether IP-10 levels predict treatment in acute HCV infection is unknown.
Methods
Patients with acute or early chronic HCV infection from the Australian Trial in Acute Hepatitis C (ATAHC) cohort were evaluated. Baseline and on-treatment plasma IP-10 levels were measured by ELISA. IL28B genotype was determined by sequencing.
Results
Overall, 74 HCV mono-infected and 35 HIV/HCV co-infected patients were treated in ATAHC, of whom 89 were adherent to therapy and were included for analysis. IP-10 levels correlated with HCV RNA levels at baseline (r = 0.48, P<0.001) and during treatment. Baseline IP-10 levels were higher in patients who failed to achieve rapid virological response (RVR). Only one patient with a plasma IP-10 level >600 pg/mL achieved RVR. There was no association with IP-10 levels and early virological response (EVR) or sustained virological response (SVR).
Conclusions
Baseline IP-10 levels are associated with early viral kinetics but not ultimate treatment outcome in acute HCV infection. Given previous data showing that patients with high baseline IP-10 are unlikely to spontaneously clear acute HCV infection, they should be prioritized for early antiviral therapy.
doi:10.1371/journal.pone.0080003
PMCID: PMC3835825  PMID: 24278230
18.  Impaired Hepatitis C Virus (HCV)–Specific Interferon-γ Responses in Individuals With HIV Who Acquire HCV Infection: Correlation With CD4+ T-Cell Counts 
The Journal of Infectious Diseases  2012;206(10):1568-1576.
Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4+ T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534).
doi:10.1093/infdis/jis544
PMCID: PMC3475632  PMID: 22949308
19.  The chlamydia knowledge, awareness and testing practices of Australian general practitioners and practice nurses: survey findings from the Australian Chlamydia Control Effectiveness Pilot (ACCEPt) 
BMC Family Practice  2013;14:169.
Background
ACCEPt, a large cluster randomized control trial, aims to determine if annual testing for 16 to 29 year olds in general practice can reduce chlamydia prevalence. ACCEPt is the first trial investigating the potential role of practice nurses (PN) in chlamydia testing. To inform the design of the ACCEPt intervention, we aimed to determine the chlamydia knowledge, attitudes, and testing practices of participating general practitioners (GPs) and PNs.
Methods
GPs and PNs from 143 clinics recruited from 52 areas in 4 Australian states were asked to complete a survey at time of recruitment. Responses of PNs and GPs were compared using conditional logistic regression to account for possible intra cluster correlation within clinics.
Results
Of the PNs and GPs enrolled in ACCEPt, 81% and 72% completed the questionnaire respectively. Less than a third of PNs (23%) and GPs (32%) correctly identified the two age groups with highest infection rates in women and only 16% vs 17% the correct age groups in men. More PNs than GPs would offer testing opportunistically to asymptomatic patients aged ≤25 years; women having a pap smear (84% vs 55%, P<0.01); antenatal checkup (83% vs 44%, P<0.01) and Aboriginal men with a sore throat (79% vs 33%, P<0.01), but also to patients outside of the guideline age group at the time of the survey; 26 year old males presenting for a medical check (78% vs 30%, P = <0.01) and 33 year old females presenting for a pill prescription (83% vs 55%, P<0.01). More PNs than GPs knew that retesting was recommended after chlamydia treatment (93% vs 87%, P=0.027); and the recommended timeframe was 3 months (66% vs 26%, P<0.01). A high proportion of PNs (90%) agreed that they could conduct chlamydia testing in general practice, with 79% wanting greater involvement and 89% further training.
Conclusions
Our survey reveals gaps in chlamydia knowledge and management among GPs and PNs that may be contributing to low testing rates in general practice. The ACCEPt intervention is well targeted to address these and support clinicians in increasing testing rates. PNs could have a role in increasing chlamydia testing.
doi:10.1186/1471-2296-14-169
PMCID: PMC3827502  PMID: 24219113
20.  Outreach for chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes 
BMC Public Health  2013;13:1040.
Background
High Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence have been reported in populations that do not regularly access health centres for sexually transmissible infections (STI) testing. We reviewed current outreach strategies used to increase access to STI testing and their outcomes.
Methods
We systematically reviewed the literature for English language studies published between 1 January 2005 and 28 January 2011 describing CT and/or NG screening programs in non-clinical outreach settings.
Results
We identified 25 programs, with the majority occurring in either Australia (32%) or the United States (32%). The most common target groups were young people aged 15–29 years (52%), men who have sex with men (24%) and sex workers (8%). The median CT positivity was 7.7% (Inter Quartile Range [IQR]: 3.0%-11.1%, n=19 programs), and median NG positivity was 2.6% (IQR: 0.0%-8.0%, n=10). The median participation rate was 53% (IQR: 23.9%-81.3%), and a median of 79.6% (IQR: 55.1%-89.4%) of participants were tested, with a median of 100 tests conducted per program (IQR: 65–331, range: 11–1808). Across all settings the participation rate was highest among target groups gathering in community service venues (community centres, parenting centres, homeless shelters) (median=81.4%, n=4), and social venues (sporting venues or bars) (80.4%, n=1). Lower participation rates were found in street/public community areas (median=23.9%, n=3) and sex on premises venues (10.4% and 24.3%, n=2).
Conclusions
The review indicated that although CT and NG outreach programs reached a relatively small number of people the yield of infections is high. Settings which appear to be more effective at encouraging participation appear to be those within an existing venue, rather than in public areas.
doi:10.1186/1471-2458-13-1040
PMCID: PMC3819260  PMID: 24188541
Sexually transmissible infections; Outreach; Testing; Systematic review; Chlamydia
21.  A randomised trial of point-of-care tests for chlamydia and gonorrhoea infections in remote Aboriginal communities: Test, Treat ANd GO- the “TTANGO” trial protocol 
BMC Infectious Diseases  2013;13:485.
Background
High prevalence rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) have been reported in Aboriginal people in remote and regional areas of Australia for well over two decades, and repeat positivity rates are high. To interrupt disease transmission and reduce the risk of complications, early diagnosis and treatment is important. However in many remote and regional areas there are long delays between testing for these curable sexually transmissible infections and providing treatment, due to both physical distance from laboratories and difficulties when recalling patients for subsequent management once results are available. Point-of-care (POC) tests have the potential to provide more timely diagnosis, to increase treatment and contact tracing, and in turn reduce CT and NG infection rates.
Methods/design
TTANGO (Test, Treat, ANd GO) is a cross-over cluster randomised controlled trial in 12 regional or remote Australian health services, which predominantly provide clinical services to Aboriginal people. The overall aim of TTANGO is to measure the clinical effectiveness, cost-effectiveness and cultural and operational acceptability of molecular POC testing for CT and NG infection. The primary outcome is repeat positivity at three months after treatment of an initial CT or NG infection.
Participating health services will undertake the clinical management of CT and NG under two different modalities for one year each. In the first year, six health services will be randomly assigned to manage these infections under current diagnostic guidelines. The other six will supplement current diagnostic guidelines with POC testing, whereby diagnosis is made and subsequent treatment for those with positive POC tests is offered at the initial consultation. In the second year, the health services will cross over to the opposite management modality.
TTANGO will be conducted over four years; 1.5 years of trial initiation and community consultation, 2 years of trial conditions and evaluation, and 6 months of data analysis and feedback.
Discussion
TTANGO is the first cluster randomised trial of POC testing for CT and NG internationally. The results of this trial will provide crucial information to guide sexual health clinical practice in remote Aboriginal communities and other high prevalence settings.
Trial registration
Australian and New Zealand Clinical Trials Registry ACTRN12613000808741
doi:10.1186/1471-2334-13-485
PMCID: PMC4231474  PMID: 24138699
Point-of-care testing; Sexually transmitted infections; Randomized controlled trial
22.  Foreskin cutting beliefs and practices and the acceptability of male circumcision for HIV prevention in Papua New Guinea 
BMC Public Health  2013;13:818.
Background
Male circumcision (MC) reduces HIV acquisition and is a key public health intervention in settings with high HIV prevalence, heterosexual transmission and low MC rates. In Papua New Guinea (PNG), where HIV prevalence is 0.8%, there is no medical MC program for HIV prevention. There are however many different foreskin cutting practices across the country’s 800 language groups. The major form exposes the glans but does not remove the foreskin. This study aimed to describe and quantify foreskin cutting styles, practices and beliefs. It also aimed to assess the acceptability of MC for HIV prevention in PNG.
Methods
Cross-sectional multicentre study, at two university campuses (Madang Province and National Capital District) and at two ‘rural development’ sites (mining site Enga Province; palm-oil plantation in Oro Province). Structured questionnaires were completed by participants originating from all regions of PNG who were resident at each site for study or work.
Results
Questionnaires were completed by 861 men and 519 women. Of men, 47% reported a longitudinal foreskin cut (cut through the dorsal surface to expose the glans but foreskin not removed); 43% reported no foreskin cut; and 10% a circumferential foreskin cut (complete removal). Frequency and type of cut varied significantly by region of origin (p < .001). Most men (72-82%) were cut between the ages of 10 – 20 years. Longitudinal cuts were most often done in a village by a friend, with circumferential cuts most often done in a clinic by a health professional. Most uncut men (71%) and longitudinal cut men (84%) stated they would remove their foreskin if it reduced the risk of HIV infection. More than 95% of uncut men and 97% of longitudinal cut men would prefer the procedure in a clinic or hospital. Most men (90%) and women (74%) stated they would remove the foreskin of their son if it reduced the risk of HIV infection.
Conclusion
Although 57% of men reported some form of foreskin cut only 10% reported the complete removal of the foreskin, the procedure on which international HIV prevention strategies are based. The acceptability of MC (complete foreskin removal) is high among men (for themselves and their sons) and women (for their sons). Potential MC services need to be responsive to the diversity of beliefs and practices and consider health system constraints. A concerted research effort to investigate the potential protective effects of longitudinal cuts for HIV acquisition is essential given the scale of longitudinal cuts in PNG.
doi:10.1186/1471-2458-13-818
PMCID: PMC3846639  PMID: 24015786
Male circumcision; Acceptability; Foreskin cutting; Papua New Guinea; HIV; Prevention; Beliefs; Foreskin cutting practices; Longitudinal Foreskin cut; Circumferential Foreskin cut
23.  STI in remote communities: improved and enhanced primary health care (STRIVE) study protocol: a cluster randomised controlled trial comparing ‘usual practice’ STI care to enhanced care in remote primary health care services in Australia 
BMC Infectious Diseases  2013;13:425.
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
doi:10.1186/1471-2334-13-425
PMCID: PMC3847940  PMID: 24016143
Aboriginal; Indigenous; Sexually transmitted infections; Chlamydia; Gonorrhoea; Trichomonas; Continuous quality improvement; Protocol; Prevalence; Remote
24.  Sex work and HIV in Cambodia: trajectories of risk and disease in two cohorts of high-risk young women in Phnom Penh, Cambodia 
BMJ Open  2013;3(9):e003095.
Objectives
HIV prevalence among Cambodian female sex workers (FSW) is among the highest in Southeast Asia. We describe HIV prevalence and associated risk exposures in FSW sampled serially in Phnom Penh, Cambodia (Young Women's Health Study (YWHS)), before and after the implementation of a new law designed to combat human trafficking and sexual exploitation.
Design
Cross-sectional analysis of baseline data from two prospective cohorts.
Setting
Community-based study in Phnom Penh, Cambodia.
Participants
Women aged 15–29 years, reporting ≥2 sexual partners in the last month and/or engaged in transactional sex in the last 3 months, were enrolled in the studies in 2007 (N=161; YWHS-1), and 2009 (N=220; YWHS-2) following information sessions where 285 and 345 women attended.
Primary outcomes
HIV prevalence, sexual risk behaviour, amphetamine-type stimulant (ATS) and alcohol use, and work-related factors were compared in the two groups, enrolled before and after implementation of the new law.
Results
Participants in the two cohorts were similar in age (median 25 years), but YWHS-2 women reported fewer sex partners, more alcohol use and less ATS use. A higher proportion of YWHS-2 compared with YWHS-1 women worked in entertainment-based venues (68% vs 31%, respectively). HIV prevalence was significantly lower in the more recently sampled women: 9.2% (95% CI 4.5% to 13.8%) vs 23% (95% CI 16.5% to 29.7%).
Conclusions
Sex work context and risk have shifted among young FSW in Phnom Penh, following implementation of anti-prostitution and anti-trafficking laws. While both cohorts were recruited using the same eligibility criteria, more recently sampled women had lower prevalence of sexual risk and HIV infection. Women engaging more directly in transactional sex have become harder to sample and access. Future prevention research and programmes need to consider how new policies and demographic changes in FSW impact HIV transmission.
doi:10.1136/bmjopen-2013-003095
PMCID: PMC3773643  PMID: 24022389
EPIDEMIOLOGY
25.  Listening to diverse community voices: the tensions of responding to community expectations in developing a male circumcision program for HIV prevention in Papua New Guinea 
BMC Public Health  2013;13:749.
Background
The success of health programs is influenced not only by their acceptability but also their ability to meet and respond to community expectations of service delivery. The World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) have recommended medical male circumcision (MC) as an essential component of comprehensive HIV prevention programs in high burden settings. This study investigated community-level perceptions of MC for HIV prevention in Papua New Guinea (PNG), a setting where diverse traditional and contemporary forms of penile foreskin cutting practices have been described.
Methods
A multi-method qualitative study was undertaken in four provinces in two stages from 2009 to 2011. A total of 82 in-depth interviews, and 45 focus group discussions were completed during Stage 1. Stage 2 incorporated eight participatory workshops that were an integral part of the research dissemination process to communities. The workshops also provided opportunity to review key themes and consolidate earlier findings as part of the research process. Qualitative data analysis used a grounded theory approach and was facilitated using qualitative data management software.
Results
A number of diverse considerations for the delivery of MC for HIV prevention in PNG were described, with conflicting views both between and within communities. Key issues included: location of the service, service provider, age eligibility, type of cut, community awareness and potential shame amongst youth. Key to developing appropriate health service delivery models was an appreciation of the differences in expectations and traditions of unique cultural groups in PNG. Establishing strong community coalitions, raising awareness and building trust were seen as integral to success.
Conclusions
Difficulties exist in the implementation of new programs in a pluralistic society such as PNG, particularly if tensions arise between biomedical knowledge and medico-legal requirements, compared to existing socio-cultural interests. Community participatory approaches offer important opportunities to explore and design culturally safe, specific and accessible programs.
doi:10.1186/1471-2458-13-749
PMCID: PMC3751450  PMID: 23941536
Community participation; Male circumcision; Penile cutting; HIV

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