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1.  Multi-Centre Evaluation of the Determine HIV Combo Assay when Used for Point of Care Testing in a High Risk Clinic-Based Population 
PLoS ONE  2014;9(4):e94062.
Background
Determine HIV Combo (DHC) is the first point of care assay designed to increase sensitivity in early infection by detecting both HIV antibody and antigen. We conducted a large multi-centre evaluation of DHC performance in Sydney sexual health clinics.
Methods
We compared DHC performance (overall, by test component and in early infection) with conventional laboratory HIV serology (fourth generation screening immunoassay, supplementary HIV antibody, p24 antigen and Western blot tests) when testing gay and bisexual men attending four clinic sites. Early infection was defined as either acute or recent HIV infection acquired within the last six months.
Results
Of 3,190 evaluation specimens, 39 were confirmed as HIV-positive (12 with early infection) and 3,133 were HIV-negative by reference testing. DHC sensitivity was 87.2% overall and 94.4% and 0% for the antibody and antigen components, respectively. Sensitivity in early infection was 66.7% (all DHC antibody reactive) and the DHC antigen component detected none of nine HIV p24 antigen positive specimens. Median HIV RNA was higher in false negative than true positive cases (238,025 vs. 37,591 copies/ml; p = 0.022). Specificity overall was 99.4% with the antigen component contributing to 33% of false positives.
Conclusions
The DHC antibody component detected two thirds of those with early infection, while the DHC antigen component did not enhance performance during point of care HIV testing in a high risk clinic-based population.
doi:10.1371/journal.pone.0094062
PMCID: PMC3979750  PMID: 24714441
2.  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
3.  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
4.  Analytical Evaluation of GeneXpert CT/NG, the First Genetic Point-of-Care Assay for Simultaneous Detection of Neisseria gonorrhoeae and Chlamydia trachomatis 
Journal of Clinical Microbiology  2013;51(6):1945-1947.
GeneXpert CT/NG was evaluated with 372 characterized bacterial strains. Sensitivity of 10 genome copies/reaction was obtained for both agents. Four Neisseria mucosa and two Neisseria subflava isolates were positive for one of two gonococcal targets; however, the assay flagged all as negative. The assay was analytically highly sensitive and specific.
doi:10.1128/JCM.00806-13
PMCID: PMC3716077  PMID: 23554203
5.  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
6.  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
7.  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
8.  Chronic hepatitis B prevalence among Aboriginal and Torres Strait Islander Australians since universal vaccination: a systematic review and meta-analysis 
BMC Infectious Diseases  2013;13:403.
Background
In Australia, higher rates of chronic hepatitis B (HBsAg) have been reported among Aboriginal and Torres Strait Islander (Indigenous) compared with non-Indigenous people. In 2000, the Australian government implemented a universal infant/adolescent hepatitis B vaccination program. We undertook a systematic review and meta-analysis to assess the disparity of HBsAg prevalence between Indigenous and non-Indigenous people, particularly since 2000.
Methods
We searched Medline, Embase and public health bulletins up to March 2011. We used meta-analysis methods to estimate HBsAg prevalence by Indigenous status and time period (before and since 2000).
Results
There were 15 HBsAg prevalence estimates (from 12 studies) among Indigenous and non-Indigenous people; adults and pregnant women (n = 9), adolescents (n = 3), prisoners (n = 2), and infants (n = 1). Of these, only one subgroup (adults/pregnant women) involved studies before and since 2000 and formed the basis of the meta-analysis. Before 2000, the pooled HBsAg prevalence estimate was 6.47% (95% CI: 4.56-8.39); 16.72% (95%CI: 7.38-26.06) among Indigenous and 0.36% (95%CI:-0.14-0.86) in non-Indigenous adults/pregnant women. Since 2000, the pooled HBsAg prevalence was 2.25% (95% CI: 1.26-3.23); 3.96% (95%CI: 3.15-4.77) among Indigenous and 0.90% (95% CI: 0.53-1.28) in non-Indigenous adults/pregnant women.
Conclusions
The disparity of HBsAg prevalence between Indigenous and non-Indigenous people has decreased over time; particularly since the HBV vaccination program in 2000. However HBsAg prevalence remains four times higher among Indigenous compared with non-Indigenous people. The findings highlight the need for opportunistic HBV screening of Indigenous people to identify people who would benefit from vaccination or treatment.
doi:10.1186/1471-2334-13-403
PMCID: PMC3846608  PMID: 24004727
Indigenous; HBV; Sexually transmissible infection; STI; Hepatitis
9.  Opt-Out and Opt-In Testing Increases Syphilis Screening of HIV-Positive Men Who Have Sex with Men in Australia 
PLoS ONE  2013;8(8):e71436.
Background
Since 2005, Australian clinicians were advised to undertake quarterly syphilis testing for all sexually active HIV-positive men who have sex with men (MSM). We describe differences in syphilis testing frequency among HIV-positive MSM by clinic testing policies since this recommendation.
Methods
Three general practices, two sexual health clinics and two hospital HIV outpatient clinics provided data on HIV viral load and syphilis testing from 2006–2010. Men having ≥1 viral load test per year were included; >95% were MSM. We used Chi-2 tests to assess changes in syphilis testing frequency over time, and differences by clinic testing policy (opt-out, opt-in and risk-based).
Results
The proportion of men having HIV viral loads with same-day syphilis tests increased from 37% in 2006 to 63% in 2007 (p<0.01) and 68–69% thereafter. In 2010, same-day syphilis testing was highest in four clinics with opt-out strategies (87%, range:84–91%) compared with one clinic with opt-in (74%, p = 0.121) and two clinics with risk-based strategies (22%, range:20–24%, p<0.01). The proportion of men having ≥3 syphilis tests per year increased from 15% in 2006 to 36% in 2007 (p<0.01) and 36–38% thereafter. In 2010, the proportion of men having ≥3 syphilis tests in a year was highest in clinics with opt-out strategies (48%, range:35–59%), compared with opt-in (39%, p = 0.121) and risk-based strategies (8.4%, range:5.4–12%, p<0.01).
Conclusion
Over five years the proportion of HIV-positive men undergoing syphilis testing at recommended frequencies more than doubled, and was 5–6 times higher in clinics with opt-out and opt-in strategies compared with risk-based policies.
doi:10.1371/journal.pone.0071436
PMCID: PMC3751889  PMID: 24009661
10.  Automated, Computer Generated Reminders and Increased Detection of Gonorrhoea, Chlamydia and Syphilis in Men Who Have Sex with Men 
PLoS ONE  2013;8(4):e61972.
Background
Guidelines recommend frequent screening of men who have sex with men (MSM) for sexually transmissible infections (STIs) but few interventions have demonstrated increased testing and detection of bacterial STIs among MSM in controlled studies.
Methods
We used automated text message and email reminders generated by computer assisted self-interview (CASI) to remind MSM to retest for syphilis. We compared clinic visits, STI testing and detection rates over 12 month between men receiving reminders (reminder group) and men not offered the reminders (concurrent control group).
Results
Men who chose 3-monthly reminders had more clinic visits (median 3 vs 1) and higher testing rates for pharyngeal gonorrhoea (67.0% vs 33.6%), rectal gonorrhoea (62.7% vs 31.1%), urethral chlamydia (67.3% vs 39.3%), rectal chlamydia (62.9% vs 31.3%), syphilis (67.0% vs 39.3%) and HIV (64.9% vs 36.7%) (all p<0.001) than concurrent controls, within 12 months after their first visit. Also, men receiving reminders had a higher combined testing rate for all the aforementioned STIs at a same visit (55.7% vs 25.5%, p<0.001) compared with concurrent controls. This association remained after adjusting for differences in characteristics between the two groups (adjusted odds ratio:1.77, 95% confidence interval:1.51-2.08). Men receiving reminders also had a higher detection rate of: rectal gonorrhoea (3.7% vs 1.2%, p = 0.001), urethral chlamydia (3.1% vs 1.4%, p = 0.027), rectal chlamydia (6.6% vs 2.8%, p<0.001), and early, latent syphilis (1.7% vs 0.4%, p = 0.008) compared with concurrent controls.
Conclusion
This is the first study to demonstate that a fully automated reminder system using CASI was associated with increased detection of bacterial STIs among MSM.
doi:10.1371/journal.pone.0061972
PMCID: PMC3629129  PMID: 23613989
11.  Decline in in-patient treatments of genital warts among young Australians following the national HPV vaccination program 
BMC Infectious Diseases  2013;13:140.
Background
There has been a rapid decline in the number of young heterosexuals diagnosed with genital warts at outpatient sexual health services since the national human papillomavirus (HPV) vaccination program started in Australia in 2007. We assessed the impact of the vaccination program on the number of in-patient treatments for genital warts.
Methods
Data on in-patient treatments of genital warts in all private hospitals were extracted from the Medicare website. Medicare is the universal health insurance scheme of Australia. In the vaccine period (2007–2011) and pre-vaccine period (2000–2007) we calculated the percentage change in treatment numbers and trends in annual treatment rates in private hospitals. Australian population data were used to calculate rates. Summary rate ratios of average annual trends were determined.
Results
Between 2000 and 2011, 6,014 women and 936 men aged 15–44 years underwent in-patient treatment for genital warts in private hospitals. In 15–24 year old women, there was a significant decreasing trend in annual treatment rates of vulval/vaginal warts in the vaccine period (overall decrease of 85.3% in treatment numbers from 2007 to 2011) compared to no significant trend in the pre-vaccine period (summary rate ratio (SRR) = 0.33, p < 0.001). In 25–34 year old women, declining trends were seen in both vaccine and pre-vaccine periods (overall decrease of 33% vs. 24.3%), but the rate of change was greater in the vaccine period (SRR = 0.60, p < 0.001). In 35–44 year old women, there was no significant change in both periods (SRR = 0.91, p = 0.14). In 15–24 year old men, there was a significant decreasing trend in annual treatment rates of penile warts in the vaccine period (decrease of 70.6%) compared to an increasing trend in the pre-vaccine period (SRR = 0.76, p = 0.02). In 25–34 year old men there was a significant decreasing trend in the vaccine period compared to no change in the pre-vaccine period (SRR = 0.81, p = 0.04) and in 35–44 year old men there was no significant change in rates of penile warts both periods, but the rate of change was greater in the vaccine period (SRR = 0.70, p = 0.02).
Conclusions
The marked decline in in-patient treatment of vulval/vaginal warts in the youngest women is probably attributable to the HPV vaccine program. The moderate decline in in-patient treatments for penile warts in men probably reflects herd immunity.
doi:10.1186/1471-2334-13-140
PMCID: PMC3606327  PMID: 23506489
12.  Home-based chlamydia and gonorrhoea screening: a systematic review of strategies and outcomes 
BMC Public Health  2013;13:189.
Background
In many countries, low Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) screening rates among young people in primary-care have encouraged screening programs outside of clinics. Nucleic acid amplification tests (NAATs) make it possible to screen people in homes with self-collected specimens. We systematically reviewed the strategies and outcomes of home-based CT/NG screening programs.
Methods
Electronic databases were searched for home-based CT and/or NG screening studies published since January 2005. Screening information (e.g. target group, recruitment and specimen-collection method) and quantitative outcomes (e.g. number of participants, tests and positivity) were extracted. The screening programs were classified into seven groups on the basis of strategies used.
Results
We found 29 eligible papers describing 32 home-based screening programs. In seven outreach programs, people were approached in their homes: a median of 97% participants provided specimens and 76% were tested overall (13717 tests). In seven programs, people were invited to receive postal test-kits (PTKs) at their homes: a median of 37% accepted PTKs, 79% returned specimens and 19% were tested (46225 tests). PTKs were sent along with invitation letters in five programs: a median of 33% returned specimens and 29% of those invited were tested (15126 tests). PTKs were requested through the internet or phone without invitations in four programs and a median of 32% returned specimens (2666 tests). Four programs involved study personnel directly inviting people to receive PTKs: a median of 46% accepted PTKs, 21% returned specimens and 9.1% were tested (341 tests). PTKs were picked-up from designated locations in three programs: a total of 6765 kits were picked-up and 1167 (17%) specimens were returned for screening. Two programs used a combination of above strategies (2395 tests) but the outcomes were not reported separately. The overall median CT positivity was 3.6% (inter-quartile range: 1.7-7.3%).
Conclusions
A variety of strategies have been used in home-based CT/NG screening programs. The screening strategies and their feasibility in the local context need to be carefully considered to maximize the effectiveness of home-based screening programs.
doi:10.1186/1471-2458-13-189
PMCID: PMC3599833  PMID: 23496833
Sexually transmitted infections; Chlamydia trachomatis; Screening; Home
13.  A longitudinal evaluation of Treponema pallidum PCR testing in early syphilis 
BMC Infectious Diseases  2012;12:353.
Background
Syphilis is a growing public health problem among men who have sex with men (MSM) globally. Rapid and accurate detection of syphilis is vital to ensure patients and their contacts receive timely treatment and reduce ongoing transmission.
Methods
We evaluated a PCR assay for the diagnosis of Treponema pallidum using swabs of suspected early syphilis lesions in longitudinally assessed MSM.
Results
We tested 260 MSM for T pallidum by PCR on 288 occasions: 77 (26.7%) had early syphilis that was serologically confirmed at baseline or within six weeks, and 211 (73.3%) remained seronegative for syphilis. Of 55 men with primary syphilis, 49 were PCR positive, giving a sensitivity of 89.1% (95% CI: 77.8%-95.9%) and a specificity of 99.1% (95% CI: 96.5%-99.9%). Of 22 men with secondary syphilis, 11 were PCR positive, giving a sensitivity of 50% (95% CI: 28.2%-71.8%) and a specificity of 100% (95% CI: 66.4%-71.8%). Of the 77 syphilis cases, 43 (56%) were HIV positive and the sensitivity and specificity of the PCR test did not vary by HIV status. The PCR test was able to detect up to five (10%) primary infections that were initially seronegative, including one HIV positive man with delayed seroconversion to syphilis (72 to 140 days) and one HIV positive man who did not seroconvert to syphilis over 14 months follow-up. Both men had been treated for syphilis within a week of the PCR test.
Conclusions
T pallidum PCR is a potentially powerful tool for the early diagnosis of primary syphilis, particularly where a serological response has yet to develop.
doi:10.1186/1471-2334-12-353
PMCID: PMC3541217  PMID: 23241398
Syphilis; PCR; Evaluation
14.  Improving Adherence to Guidelines for the Diagnosis and Management of Pelvic Inflammatory Disease: A Systematic Review 
Background. Evidence suggests adherence to clinical guidelines for pelvic inflammatory disease (PID) diagnosis and management is suboptimal. We systematically reviewed the literature for studies describing strategies to improve the adherence to PID clinical guidelines. Methods. The databases MEDLINE and EMBASE, and reference lists of review articles were searched from January 2000 to April 2012. Only studies with a control group were included. Results. An interrupted time-series study and two randomised controlled trials (RCTs) were included. The interrupted time-series found that following a multifaceted patient and practitioner intervention (practice protocol, provision of antibiotics on-site, written instructions for patients, and active followup), more patients received the recommended antibiotics and attended for followup. One RCT found a patient video on PID self-care did not improve medication compliance and followup. Another RCT found an abbreviated PID treatment guideline for health-practitioners improved their management of PID in hypothetical case scenarios but not their diagnosis of PID. Conclusion. There is limited research on what strategies can improve practitioner and patient adherence to PID diagnosis and management guidelines. Interventions that make managing PID more convenient, such as summary guidelines and provision of treatment on-site, appear to lead to better adherence but further empirical evidence is necessary.
doi:10.1155/2012/325108
PMCID: PMC3437626  PMID: 22973085
15.  The prevalence of Chlamydia trachomatis infection in Australia: a systematic review and meta-analysis 
BMC Infectious Diseases  2012;12:113.
Background
Chlamydia trachomatis is a common sexually transmitted infection in Australia. This report aims to measure the burden of chlamydia infection by systematically reviewing reports on prevalence in Australian populations.
Methods
Electronic databases and conference websites were searched from 1997–2011 using the terms ‘Chlamydia trachomatis’ OR ‘chlamydia’ AND ‘prevalence’ OR ‘epidemiology’ AND ‘Australia’. Reference lists were checked and researchers contacted for additional literature. Studies were categorised by setting and participants, and meta-analysis conducted to determine pooled prevalence estimates for each category.
Results
Seventy-six studies met the inclusion criteria for the review. There was a high level of heterogeneity between studies; however, there was a trend towards higher chlamydia prevalence in younger populations, Indigenous Australians, and those attending sexual health centres. In community or general practice settings, pooled prevalence for women <25 years in studies conducted post-2005 was 5.0% (95% CI: 3.1, 6.9; five studies), and for men <30 years over the entire review period was 3.9% (95% CI: 2.7, 5.1; six studies). For young Australians aged <25 years attending sexual health, family planning or youth clinics, estimated prevalence was 6.2% (95% CI: 5.1, 7.4; 10 studies) for women and 10.2% (95% CI: 9.5, 10.9; five studies) for men. Other key findings include pooled prevalence estimates of 22.1% (95% CI: 19.0, 25.3; three studies) for Indigenous women <25 years, 14.6% (95% CI: 11.5, 17.8; three studies) for Indigenous men <25 years, and 5.6% (95% CI: 4.8, 6.3; 11 studies) for rectal infection in men who have sex with men. Several studies failed to report basic demographic details such as sex and age, and were therefore excluded from the analysis.
Conclusions
Chlamydia trachomatis infections are a significant health burden in Australia; however, accurate estimation of chlamydia prevalence in Australian sub-populations is limited by heterogeneity within surveyed populations, and variations in sampling methodologies and data reporting. There is a need for more large, population-based studies and prospective cohort studies to compliment mandatory notification data.
doi:10.1186/1471-2334-12-113
PMCID: PMC3462140  PMID: 22583480
Chlamydia; Meta-analysis; Prevalence; Systematic review
16.  Efficacy of interventions to increase the uptake of chlamydia screening in primary care: a systematic review 
BMC Infectious Diseases  2011;11:211.
Background
As most genital chlamydia infections are asymptomatic, screening is the main way to detect and cases for treatment. We undertook a systematic review of studies assessing the efficacy of interventions for increasing the uptake of chlamydia screening in primary care.
Methods
We reviewed studies which compared chlamydia screening in the presence and the absence of an intervention. The primary endpoints were screening rate or total tests.
Results
We identified 16 intervention strategies; 11 were randomised controlled trials and five observational studies, 10 targeted females only, five both males and females, and one males only. Of the 15 interventions among females, six were associated with significant increases in screening rates at the 0.05 level including a multifaceted quality improvement program that involved provision of a urine jar to patients at registration (44% in intervention clinics vs. 16% in the control clinic); linking screening to routine Pap smears (6.9% vs. 4.5%), computer alerts for doctors (12.2% vs. 10.6%); education workshops for clinic staff; internet-based continuing medical education (15.5% vs. 12.4%); and free sexual health consultations (16.8% vs. 13.2%). Of the six interventions targeting males, two found significant increases including the multifaceted quality improvement program in which urine jars were provided to patients at registration (45% vs. 15%); and the offering by doctors of a test to all presenting young male clients, prior to consultation (29 vs. 4%).
Conclusions
Interventions that promoted the universal offer of a chlamydia test in young people had the greatest impact on increasing screening in primary care.
doi:10.1186/1471-2334-11-211
PMCID: PMC3176492  PMID: 21816113
17.  Using population attributable risk to choose HIV prevention strategies in men who have sex with men 
BMC Public Health  2011;11:247.
Background
In Australia, HIV is concentrated in men who have sex with men (MSM) and rates have increased steadily over the past ten years. Health promotion strategies should ideally be informed by an understanding of both the prevalence of the factors being modified, as well as the size of the risk that they confer. We undertook an analysis of the potential population impact and cost saving that would likely result from modifying key HIV risk factors among men who have sex with men (MSM) in Sydney, Australia.
Methods
Proportional hazard analyses were used to examine the association between sexual behaviours in the last six months and sexually transmissible infections on HIV incidence in a cohort of 1426 HIV-negative MSM who were recruited primarily from community-based sources between 2001 and 2004 and followed to mid-2007. We then estimated the proportion of HIV infections that would be prevented if specific factors were no longer present in the population, using a population attributable risk (PAR) method which controls for confounding among factors. We also calculated the average lifetime healthcare costs incurred by the HIV infections associated with specific factors by estimating costs associated with clinical care and treatment following infection and discounting at 3% (1% and 5% sensitivity) to present value.
Results
Unprotected anal intercourse (UAI) with a known HIV-positive partner was reported by 5% of men, the hazard ratio (HR) was 16.1 (95%CI:6.4-40.5), the PAR was 34% (95%CI:24-44%) and the average lifetime HIV-related healthcare costs attributable to UAI with HIV-positive partners were $AUD102 million (uncertainty range: $93-114 m). UAI with unknown HIV status partners was reported by 25% of men, the HR was 4.4 (95%CI:1.8-11.2), the PAR was 33% (95%CI:26-42%) and the lifetime incurred costs were $AUD99 million. Anal warts prevalence was 4%, the HR was 5.2 (95%CI:2.4-11.2), the PAR was 13% (95%CI:9-19%) and the lifetime incurred costs were $AUD39 million.
Conclusions
Our analysis has found that although UAI with an HIV-positive sexual partner is a relatively low-prevalence behaviour (reported by 5% of men), if this behaviour was not present in the population, the number of infections would be reduced by one third. No other single behaviour or sexually transmissible infections contributes to a greater proportion of infections and HIV-related healthcare costs.
doi:10.1186/1471-2458-11-247
PMCID: PMC3100254  PMID: 21504574
18.  Population attributable risk for chlamydia infection in a cohort of young international travellers (backpackers) and residents in Australia 
BMJ Open  2011;1(1):e000004.
Aim
To estimate the population attributable risk (PAR) for Chlamydia trachomatis infection in young men and women in Sydney, Australia.
Method
Multivariate logistic regression was used to examine the association between demographic, sexual behaviour and other potential risk factors and chlamydia positivity in young (≤30 years) heterosexual international travellers (backpackers) and Australian residents attending a sexual health clinic. Point and interval estimates of PAR were calculated to quantify the proportion of chlamydia infections that can theoretically be prevented if a combination of risk factors is eliminated from a target population.
Results
In males, the PAR associated with inconsistent condom use in the past 3 months was 65% (95% CI 56% to 71%) in backpackers compared to 50% (95% CI 41% to 56%) in non-backpackers and the PAR associated with reporting three or more female sexual partners in the past 3 months was similar between male backpackers and non-backpackers (33% (95% CI 28% to 40%) and 36% (95% CI 32% to 41%), respectively). In females, the PAR associated with inconsistent condom use in the past 3 months was 51% (95% CI 42% to 59%) in backpackers compared to 41% (95% CI 31% to 51%) in non-backpackers, and the PAR associated with reporting three or more male sexual partners in the past 3 months was 14% (95% CI 11% to 18%) in backpackers compared to 30% (95% CI 25% to 37%) in non-backpackers.
Conclusion
These findings suggest that the largest number of chlamydia infections could be avoided by increasing condom use, particularly in backpackers. Reporting multiple partners was also associated with a large proportion of infections and the risk associated with this behaviour should be considered in health promotion strategies.
Article summary
Article focus
Risk factors for chlamydia infection were determined among young, heterosexual backpackers and Australian residents.
A novel statistical methodology was used to investigate the potential impact of eliminating risk factors on chlamydia infection at a population level.
Key messages
Results suggest that the majority of the chlamydia infections could be avoided by increased condom use, particularly among backpackers.
Multiple sex partners in past 3 months was also associated with a high proportion of chlamydia infections at the population level.
Strengths and limitations of this study
This is the first study to investigate the potential impact of sexual risk behaviours for chlamydia infection at the population level.
The study population was sexual health clinic attendees who are likely to be at higher risk for chlamydia infection compared to the general population.
doi:10.1136/bmjopen-2010-000004
PMCID: PMC3191383  PMID: 22021720
Hepatitis C; HIV; HIV testing; homosexuality; infectious disease
19.  Developing and validating a risk scoring tool for chlamydia infection among sexual health clinic attendees in Australia: a simple algorithm to identify those at high risk of chlamydia infection 
BMJ Open  2011;1(1):e000005.
Objective
To develop and validate a risk scoring tool to identify those who are at increased risk of chlamydia infection.
Methods
We used demographic data, sexual behaviour information and chlamydia positivity results from more than 45 000 individuals who attended Sydney Sexual Health Centre between 1998 and 2009. Participants were randomly allocated to either the development or internal validation data set. Using logistic regression, we created a prediction model and weighted scoring system using the development data set and calculated the odds ratio of chlamydia positivity for participants in successively higher quintiles of score. The internal validation data set was used to evaluate the performance characteristics of the model for five quintiles of risk scores including population attributable risk, sensitivity and specificity.
Results
In the prediction model, inconsistent condom use, increased number of sexual partners in last 3 months, genital or anal symptoms and presenting to the clinic for sexually transmitted infections screening or being a contact of a sexually transmitted infection case were consistently associated with increased risk of chlamydia positivity in all groups. High scores (upper quintiles) were significantly associated with increased risk of chlamydia infection. A cut-point score of 20 or higher distinguished a increased risk group with a sensitivity of 95%, 67% and 79% among heterosexual men, women and men who have sex with men (MSM), respectively.
Conclusion
The scoring tool may be included as part of a health promotion and/or clinic website to prompt those who are at increased risk of chlamydia infection, which may potentially lead to increased uptake and frequency of testing.
Article summary
Article focus
The authors created a risk assessment tool that allows people to estimate their own chlamydia risk score based on simple non-invasive variables.
Key messages
The tool described here will potentially provide a simple and cost-effective method of identifying and alerting individuals who would benefit from chlamydia screening.
This tool may be included as part of a health promotion and/or clinic website.
This tool may potentially lead to increased uptake and frequency of testing.
Strengths and Limitations
This is the first study to utilize statistical methods to derive a locally-specific assessment tool using 12 years of data from more than 45 000 men and women.
The Study population was sexual health clinic attendees who are likely to be at higher risk for Chlamydia infection compared to the general population.
doi:10.1136/bmjopen-2010-000005
PMCID: PMC3191384  PMID: 22021721
Chlamydia infection; risk prediction; hepatitis C; HIV; HIV testing; homosexuality; infectious disease; epidemiology; sexual medicine; health informatics
20.  The use of fluorescence enhancement to improve the microscopic diagnosis of falciparum malaria 
Malaria Journal  2007;6:89.
Background
Giemsa staining of thick blood smears remains the "gold standard" for detecting malaria. However, this method is not very good for diagnosing low-level infections. A method for the simultaneous staining of Plasmodium-parasitized culture and blood smears for both bright field and fluorescence was developed and its ability to improve detection efficiency tested.
Methods
A total of 22 nucleic acid-specific fluorescent dyes were tested for their ability to provide easily observable staining of Plasmodium falciparum-parasitized red blood cells following Giemsa staining.
Results
Of the 14 dyes that demonstrated intense fluorescence staining, only SYBR Green 1, YOYO-1 and ethidum homodimer-2 could be detected using fluorescent microscopy, when cells were first stained with Giemsa. Giemsa staining was not effective when applied after the fluorescent dyes. SYBR Green 1 provided the best staining in the presence of Giemsa, as a very high percentage of the parasitized cells were simultaneously stained. When blood films were screened using fluorescence microscopy the parasites were more readily detectable due to the sharp contrast between the dark background and the specific, bright fluorescence produced by the parasites.
Conclusion
The dual staining method reported here allows fluorescence staining, which enhances the reader's ability to detect parasites under low parasitaemia conditions, coupled with the ability to examine the same cell under bright field conditions to detect the characteristic morphology of Plasmodium species that is observed with Giemsa staining.
doi:10.1186/1475-2875-6-89
PMCID: PMC1950880  PMID: 17617912
21.  Real-Time PCR Assay for Detection and Genotype Differentiation of Giardia lamblia in Stool Specimens 
Journal of Clinical Microbiology  2004;42(7):3317-3320.
Real-time PCR, using dual-labeled fluorescent probes targeting the β-giardin gene, was used to detect Giardia lamblia in human stool specimens and to discriminate between isolates from the two major genetic assemblages of G. lamblia infective to humans, assemblages A and B.
doi:10.1128/JCM.42.7.3317-3320.2004
PMCID: PMC446313  PMID: 15243104
22.  Persistence and Dissemination of Simian Retrovirus Type 2 DNA in Relation to Viremia, Seroresponse, and Experimental Transmissibility in Macaca fascicularis 
Journal of Virology  2003;77(20):10751-10759.
Endemic simian retrovirus (SRV) infection can cause fatal simian AIDS in Macaca fascicularis, but many individuals survive with few clinical signs. To further clarify the parameters of SRV pathogenesis, we investigated the persistence of viral DNA forms in relation to active viremia, antibody response, and transmissibility of infection. In M. fascicularis from endemically SRV-2-infected colonies, viral DNA was present in both linear and unintegrated long terminal repeat circular forms in peripheral blood mononuclear cells of all viremic and many nonviremic animals. Long-term followup of three individuals with distinct infection patterns demonstrated persistence of linear and circular forms of viral DNA in peripheral blood mononuclear cells and tissues, irrespective of viremia or antibody status, but reactivation of latent infections was not observed. The role of viral DNA in transmission and early pathogenesis of SRV-2 was investigated by inoculation of SRV-2 DNA-positive blood into groups of naïve M. fascicularis from either a viremic or nonviremic donor and subsequent analysis of the virological and serological status of the recipients. Transmission of SRV and development of anti-SRV antibodies were only observed in recipients of blood from the viremic donor; transfer of SRV provirus and unintegrated circular DNA in blood from the nonviremic donor did not lead to infection of the recipients. These results indicate that a proportion of M. fascicularis are able to effectively control the replication and infectivity of SRV despite long-term persistence of viral DNA forms in infected lymphocytes.
doi:10.1128/JVI.77.20.10751-10759.2003
PMCID: PMC224967  PMID: 14512525
23.  Real-Time PCR for Quantification of Giardia and Cryptosporidium in Environmental Water Samples and Sewage 
The protozoan pathogens Giardia lamblia and Cryptosporidium parvum are major causes of waterborne enteric disease throughout the world. Improved detection methods that are very sensitive and rapid are urgently needed. This is especially the case for analysis of environmental water samples in which the densities of Giardia and Cryptosporidium are very low. Primers and TaqMan probes based on the β-giardin gene of G. lamblia and the COWP gene of C. parvum were developed and used to detect DNA concentrations over a range of 7 orders of magnitude. It was possible to detect DNA to the equivalent of a single cyst of G. lamblia and one oocyst of C. parvum. A multiplex real-time PCR (qPCR) assay for simultaneous detection of G. lamblia and C. parvum resulted in comparable levels of detection. Comparison of DNA extraction methodologies to maximize DNA yield from cysts and oocysts determined that a combination of freeze-thaw, sonication, and purification using the DNeasy kit (Qiagen) provided a highly efficient method. Sampling of four environmental water bodies revealed variation in qPCR inhibitors in 2-liter concentrates. A methodology for dealing with qPCR inhibitors that involved the use of Chelex 100 and PVP 360 was developed. It was possible to detect and quantify G. lamblia in sewage using qPCR when applying the procedure for extraction of DNA from 1-liter sewage samples. Numbers obtained from the qPCR assay were comparable to those obtained with immunofluorescence microscopy. The qPCR analysis revealed both assemblage A and assemblage B genotypes of G. lamblia in the sewage. No Cryptosporidium was detected in these samples by either method.
doi:10.1128/AEM.69.9.5178-5185.2003
PMCID: PMC194944  PMID: 12957899
24.  Molecular Characterization of the Prototrophic Salmonella Mutants Defective for Intraepithelial Replication  
Infection and Immunity  2003;71(4):2247-2252.
Three MudJ prototrophs demonstrated that intracellular replication is a Salmonella virulence trait (K. Y. Leung and B. B. Finlay, Proc. Natl. Acad. Sci. USA, 88:11470-11474, 1991). mutS and mutH are disrupted in mutants 3-11 and 12-23, and ssaQ is disrupted in mutant 17-21. Further analysis revealed that loss of Salmonella pathogenicity island 2 function underlies the intracellular replication defect of 3-11 and 17-21.
doi:10.1128/IAI.71.4.2247-2252.2003
PMCID: PMC152099  PMID: 12654850

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