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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
13.  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

Results 1-13 (13)