University General - Research Publications
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ItemAntibody responses following incident anal and penile infection with human papillomavirus in teenage men who have sex with men(WILEY, 2016-08-01)Men who have sex with men (MSM) are at risk for human papillomavirus (HPV)-related anal cancer. Few data exist on antibody responses following incident anogenital infection with HPV in teenage MSM. A cohort of 200 MSM aged 16-20 years from Melbourne, Australia were assessed at baseline, 3, 6 and 12 months. At each visit anal and penile swabs were collected for HPV DNA and serum for HPV antibodies for genotypes 6, 11, 16 and 18 (Merck's Multiplex Assays using Luminex). The main outcome, seroconversion, was defined as the detection of HPV antibodies following a negative antibody result for the same HPV type at baseline. The seroincidence rates for HPV types 6, 11, 16 and 18 were: 19 (95% CI 12-26), 7 (3-12), 4 (1-8) and 6 (3-11) per 100 person-years, respectively. Men who experienced incident anal HPV infections from types 6/11 were significantly more likely to develop serum antibodies to the same HPV type(s) than those who experienced incident anal infections from types 16/18 [73 vs. 18%, odds ratio (OR) = 15, 95% CI: 2-118]. The median time between incident anal HPV infection and seroconversion for HPV 6, 11, 16 and 18 was: 91, 38, 161 and 182 days, respectively. Antibody responses against HPV types 6/11 were significantly more likely to occur following incident anal compared with incident penile infection with HPV types 6/11 (OR = 6, 95% CI: 2-21). The likelihood of antibody responses following anogenital HPV infections depends on the HPV type and site of infection.
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ItemOral Human Papillomavirus in Men Having Sex with Men: Risk-Factors and Sampling(PUBLIC LIBRARY SCIENCE, 2012-11-16)BACKGROUND: Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is becoming more common. We examined prevalence and risk factors for oral HPV among men who have sex with men (MSM) and compared sampling and transport methods. METHODS: In 2010, 500 MSM (249 HIV-positive) attending Melbourne Sexual Health Centre answered a questionnaire, swabbed their mouth and throat and collected a gargled oral rinse sample. Half the oral rinse was transported absorbed in a tampon (to enable postage). HPV was detected by polymerase chain reaction, and genotyped by Roche Linear Array®. Men with HPV 16 or 18 were retested after six months. RESULTS: Any HPV genotype was detected in 19% (95% confidence intervals (CI) 15-25%) of HIV-infected men and 7% (95% CI 4-11%) of HIV-negative men (p<0.001), and HPV 16 was detected in 4.4% (95% CI 2-8%) of HIV-infected men and 0.8% (0.1-2.8%) of HIV-negative men. Oral HPV was associated with: current smoking (adjusted odds ratio (aOR) 2.2 (95%CI: 1.2-3.9)), time since tooth-brushing (aOR per hour 0.87, 95%CI: 0.8-0.96) and number of lifetime tongue-kissing partners aOR 3.2 95%CI: (1.2-8.4) for 26-100 partners and 4.9 95%CI: (1.9-12.5) for>100 partners. Lifetime oral-penile sex partner numbers were significantly associated in a separate model: aOR 2.8(1.2-6.3) for 26-100 partners and 3.2(1.4-7.2) for>100 partners. HPV 16 and 18 persisted in 10 of 12 men after a median six months. Sensitivities of sampling methods compared to all methods combined were: oral rinse 97%, tampon-absorbed oral rinse 69%, swab 32%. CONCLUSIONS: Oral HPV was associated with HIV infection, smoking, recent tooth-brushing, and more lifetime tongue-kissing and oral sex partners. The liquid oral rinse sample was more sensitive than a tampon-absorbed oral rinse or a self-collected swab.
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ItemChlamydia trachomatis Incidence and Re-Infection among Young Women - Behavioural and Microbiological Characteristics(PUBLIC LIBRARY SCIENCE, 2012-05-25)BACKGROUND: This study aimed to estimate rates of chlamydia incidence and re-infection and to investigate the dynamics of chlamydia organism load in prevalent, incident and re-infections among young Australian women. METHODS: 1,116 women aged 16 to 25 years were recruited from primary care clinics in Australia. Vaginal swabs were collected at 3 to 6 month intervals for chlamydia testing. Chlamydia organism load was measured by quantitative PCR. RESULTS: There were 47 incident cases of chlamydia diagnosed and 1,056.34 person years of follow up with a rate of 4.4 per 100 person years (95% CI: 3.3, 5.9). Incident infection was associated with being aged 16 to 20 years [RR = 3.7 (95%CI: 1.9, 7.1)], being employed [RR = 2.4 (95%CI: 1.1, 4.9)] and having two or more new sex partners [RR = 5.5 (95%CI: 2.6, 11.7)]. Recent antibiotic use was associated with a reduced incidence [RR:0.1 (95%CI: 0.0, 0.5)]. There were 14 re-infections with a rate of 22.3 per 100 person years (95%CI: 13.2, 37.6). The median time to re-infection was 4.6 months. Organism load was higher for prevalent than incident infections (p<0.01) and for prevalent than re-infections (p<0.01). CONCLUSIONS: Chlamydia is common among young women and a high proportion of women are re-infected within a short period of time, highlighting the need for effective partner treatment and repeat testing. The difference in organism load between prevalent and incident infections suggests prevalent infection may be more important for ongoing transmission of chlamydia.
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Item'The difference in determinants of Chlamydia trachomatis and Mycoplasma genitalium in a sample of young Australian women'(BIOMED CENTRAL LTD, 2011-02-01)BACKGROUND: Differences in the determinants of Chlamydia trachomatis ('chlamydia') and Mycoplasma genitalium (MG) genital infection in women are not well understood. METHODS: A cohort study of 16 to 25 year old Australian women recruited from primary health care clinics, aimed to determine chlamydia and MG prevalence and incidence. Vaginal swabs collected at recruitment were used to measure chlamydia and MG prevalence, organism-load and chlamydia-serovar a cross-sectional analysis undertaken on the baseline results is presented here. RESULTS: Of 1116 participants, chlamydia prevalence was 4.9% (95% CI: 2.9, 7.0) (n = 55) and MG prevalence was 2.4% (95% CI: 1.5, 3.3) (n = 27). Differences in the determinants were found - chlamydia not MG, was associated with younger age [AOR:0.9 (95% CI: 0.8, 1.0)] and recent antibiotic use [AOR:0.4 (95% CI: 0.2, 1.0)], and MG not chlamydia was associated with symptoms [AOR:2.1 (95% CI: 1.1, 4.0)]. Having two or more partners in last 12 months was more strongly associated with chlamydia [AOR:6.4 (95% CI: 3.6, 11.3)] than MG [AOR:2.2 (95% CI: 1.0, 4.6)] but unprotected sex with three or more partners was less strongly associated with chlamydia [AOR:3.1 (95%CI: 1.0, 9.5)] than MG [AOR:16.6 (95%CI: 2.0, 138.0)]. Median organism load for MG was 100 times lower (5.7 × 104/swab) than chlamydia (5.6 × 106/swab) (p < 0.01) and not associated with age or symptoms for chlamydia or MG. CONCLUSIONS: These results demonstrate significant chlamydia and MG prevalence in Australian women, and suggest that the differences in strengths of association between numbers of sexual partners and unprotected sex and chlamydia and MG might be due to differences in the transmission dynamics between these infections.
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ItemMaximising retention in a longitudinal study of genital Chlamydia trachomatis among young women in Australia(BIOMED CENTRAL LTD, 2011-03-09)BACKGROUND: Cohort studies are an important study design however they are difficult to implement, often suffer from poor retention, low participation and bias. The aims of this paper are to describe the methods used to recruit and retain young women in a longitudinal study and to explore factors associated with loss to follow up. METHODS: The Chlamydia Incidence and Re-infection Rates Study (CIRIS) was a longitudinal study of Australian women aged 16 to 25 years recruited from primary health care clinics. They were followed up via the post at three-monthly intervals and required to return questionnaires and self collected vaginal swabs for chlamydia testing. The protocol was designed to maximise retention in the study and included using recruiting staff independent of the clinic staff, recruiting in private, regular communication with study staff, making the follow up as straightforward as possible and providing incentives and small gifts to engender good will. RESULTS: The study recruited 66% of eligible women. Despite the nature of the study (sexual health) and the mobility of the women (35% moved address at least once), 79% of the women completed the final stage of the study after 12 months. Loss to follow up bias was associated with lower education level [adjusted hazard ratio (AHR): 0.7 (95% Confidence Interval (CI): 0.5, 1.0)], recruitment from a sexual health centre as opposed to a general practice clinic [AHR: 1.6 (95% CI: 1.0, 2.7)] and previously testing positive for chlamydia [AHR: 0.8 (95% CI: 0.5, 1.0)]. No other factors such as age, numbers of sexual partners were associated with loss to follow up. CONCLUSIONS: The methods used were considered effective for recruiting and retaining women in the study. Further research is needed to improve participation from less well-educated women.
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ItemAzithromycin Versus Doxycycline for the Treatment of Genital Chlamydia Infection: A Meta-analysis of Randomized Controlled Trials(OXFORD UNIV PRESS INC, 2014-07-15)BACKGROUND: There has been recent debate questioning the efficacy of azithromycin for the treatment of urogenital chlamydia infection. We conducted a meta-analysis to compare the efficacy of 1 g azithromycin with 100 mg doxycycline twice daily (7 days) for the treatment of urogenital chlamydia infection. METHODS: Medline, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane reviews, and Cumulative Index to Nursing and Allied Health Literature were searched until 31 December 2013. Randomized controlled trials comparing azithromycin with doxycycline for the treatment of genital chlamydia with evaluation of microbiological cure within 3 months of treatment were included. Sex, diagnostic test, follow-up time, attrition, patient symptomatic status, and microbiological cure were extracted. The primary outcome was the difference in efficacy at final follow-up. Study bias was quantitatively and qualitatively summarized. RESULTS: Twenty-three studies were included evaluating 1147 and 912 patients for azithromycin and doxycycline, respectively. We found a pooled efficacy difference in favor of doxycycline of 1.5% (95% confidence interval [CI], -.1% to 3.1%; I(2) = 1.9%; P = .435; random effects) to 2.6% (95% CI, .5%-4.7%; fixed effects). Subgroup analyses showed that the fixed effects pooled efficacy difference for symptomatic men was 7.4% (95% CI, 2.0%-12.9%), and the random effects was 5.5% (95% CI, -1.4% to 12.4%). CONCLUSIONS: There may be a small increased efficacy of up to 3% for doxycycline compared with azithromycin for the treatment of urogenital chlamydia and about 7% increased efficacy for doxycycline for the treatment of symptomatic urethral infection in men. However, the quality of the evidence varies considerably, with few double-blind placebo-controlled trials conducted. Given increasing concern about potential azithromycin failure, further well-designed and statistically powered double-blind, placebo-controlled trials are needed.
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ItemThe efficacy of azithromycin and doxycycline for the treatment of rectal chlamydia infection: a systematic review and meta-analysis(OXFORD UNIV PRESS, 2015-05)BACKGROUND: There are increasing concerns about treatment failure following treatment for rectal chlamydia with 1 g of azithromycin. A systematic review and meta-analysis was conducted to investigate the efficacy of 1 g of azithromycin as a single dose or 100 mg of doxycycline twice daily for 7 days for the treatment of rectal chlamydia. METHODS: Medline, Embase, PubMed, Cochrane Controlled Trials Register, Australia New Zealand Clinical Trial Register and ClinicalTrials.gov were searched to the end of April 2014. Studies using 1 g of azithromycin or 7 days of doxycycline for the treatment of rectal chlamydia were eligible. Gender, diagnostic test, serovar, symptomatic status, other sexually transmitted infections, follow-up time, attrition and microbial cure were extracted. Meta-analysis was used to calculate pooled (i) azithromycin and doxycycline efficacy and (ii) efficacy difference. RESULTS: All eight included studies were observational. The random-effects pooled efficacy for azithromycin (based on eight studies) was 82.9% (95% CI 76.0%-89.8%; I(2) = 71.0%; P < 0.01) and for doxycycline (based on five studies) was 99.6% (95% CI 98.6%-100%; I(2) = 0%; P = 0.571), resulting in a random-effects pooled efficacy difference (based on five studies) of 19.9% (95% CI 11.4%-28.3%; I(2) = 48.5%; P = 0.101) in favour of doxycycline. CONCLUSIONS: The efficacy of single-dose azithromycin may be considerably lower than 1 week of doxycycline for treating rectal chlamydia. However, the available evidence is very poor. Robust randomized controlled trials are urgently required.
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ItemHigher organism load associated with failure of azithromycin to treat rectal chlamydia(CAMBRIDGE UNIV PRESS, 2016-09)Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.
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ItemTreatment efficacy of azithromycin 1 g single dose versus doxycycline 100 mg twice daily for 7 days for the treatment of rectal chlamydia among men who have sex with men - a double-blind randomised controlled trial protocol(BIOMED CENTRAL LTD, 2017-01-06)BACKGROUND: Rectal infection with Chlamydia trachomatis is one of the most common bacterial sexually transmissible infections among men who have sex with men (MSM) with diagnosis rates continuing to rise. Current treatment guidelines recommend either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. However, there are increasing concerns about treatment failure with azithromycin. We are conducting the first randomised controlled trial (RCT) to compare treatment efficacy of azithromycin versus doxycycline for the treatment of rectal chlamydia in MSM. METHODS/DESIGN: The Rectal Treatment Study will recruit 700 MSM attending Australian sexual health clinics for the treatment of rectal chlamydia. Participants will be asked to provide rectal swabs and will be randomised to either azithromycin 1 g single dose or doxycycline 100 mg twice daily for 7 days. Participants will be asked to complete questionnaires about adverse drug reactions, sexual behaviour and drug adherence via short message service and online survey. The primary outcome is the treatment efficacy as determined by a negative chlamydia nucleic acid amplification test at 4 weeks post treatment. Secondary outcomes will utilise whole genome sequencing and mRNA assay to differentiate between treatment failure, reinfection or false positive results. DISCUSSION: Rectal chlamydia is an increasing public health concern as use of pre-exposure prophylaxis against HIV becomes commonplace. Optimal, evidence-based treatment is critical to halting ongoing transmission. This study will provide the first RCT evidence comparing azithromycin and doxycycline for the treatment of rectal chlamydia. The results of this trial will establish which treatment is more efficacious and inform international management guidelines. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12614001125617.
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ItemMeasurement of tissue azithromycin levels in self-collected vaginal swabs post treatment using liquid chromatography and tandem mass spectrometry (LC-MS/MS)(PUBLIC LIBRARY SCIENCE, 2017-05-12)BACKGROUND: Azithromycin is recommended for the treatment of uncomplicated urogenital chlamydia infection although the standard 1gram dose sometimes fails to eradicate the infection (treatment failure). One hypothesis proposed for treatment failure has been insufficient levels of the antibiotic at the site of infection. We developed an assay using liquid chromatography and tandem mass spectrometry (LC-MS/MS) to measure azithromycin concentration in high-vaginal swabs and monitor how concentration changes over time following routine azithromycin treatment. METHODS: Azithromycin concentrations were measured in two groups of women either within the first 24h of taking a 1g dose (N = 11) or over 9 days (N = 10). Azithromycin concentrations were normalised to an internal standard (leucine enkephalin), and the bulk lipid species phosphatidylcholine [PC(34:1)], using an Agilent 6490 triple quadrupole instrument in positive ionisation mode. The abundances of azithromycin, PC(34:1), and leu-enkephalin were determined by multiple reaction monitoring and absolute levels of azithromycin estimated using standard curves prepared on vaginal specimens. RESULTS: Vaginal azithromycin concentrations of women were rapidly obtained after 5h post-treatment (mean concentration = 1031mcg/mg of lipid, range = 173-2693mcg/mg). In women followed for 9 days, peak concentrations were highest after day 2 (mean concentration = 2206mcg/mg, range = 721-5791mcg/mg), and remained high for at least 9 days with a mean concentration of 384mcg/mg (range = 139-1024mcg/mg) on day 9. CONCLUSION: Our study confirmed that a single 1g dose of azithromycin is rapidly absorbed and remains in the vagina at relatively high levels for at least a week, suggesting that poor antibiotic absorption is unlikely to be an explanation for treatment failure.