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Read P.,Kirketon Road Center | Read P.,University of New South Wales | Fairley C.K.,Melbourne Sexual Health Center | Fairley C.K.,Monash University | And 2 more authors.
Sexual Health | Year: 2015

Background The epidemiology of syphilis, and therefore the population most impacted, differs between countries. Many developed countries have reported an increase in syphilis notifications among men who have sex with men (MSM) over the past decade. Methods: The rates of syphilis notifications between 2000 and 2013 in the 31 countries categorised by the Organisation for Economic Co-operation and Development (OECD) as high income were investigated. Data was taken primarily from published national surveillance reports, and a male-to-female ratio substantially greater than two in syphilis notifications was taken as a proxy for the infection being disproportionately diagnosed in MSM. Results: Data was available for 27 high-income countries. The male-to-female ratio exceeded two in all but four countries. This ratio significantly increased across all geographical areas over time. Globally, the male-to-female ratio in these countries increased from 4.1 in 2000 to 7.9 in 2013 (P≤0.001). Furthermore, the proportion of male cases reported as being among MSM increased over time from 26.8% to 55.0% between 2000 and 2013 (P<0.001). Conclusion: These data show that in countries with high income, there is a near universal finding of increasing rates of syphilis in MSM. It is therefore clear that no country has identified an effective method to control syphilis in this population. © CSIRO 2015.


Machalek D.A.,University of New South Wales | Poynten M.,University of New South Wales | Jin F.,University of New South Wales | Fairley C.K.,Melbourne Sexual Health Center | And 15 more authors.
The Lancet Oncology | Year: 2012

Background: Men who have sex with men (MSM) are at greatly increased risk of human papillomavirus (HPV)-associated anal cancer. Screening for the presumed cancer precursor, high-grade anal intraepithelial neoplasia (AIN), followed by treatment in a manner analogous to cervical screening, has been proposed. We aimed to assess available data for anal HPV disease that can inform pre-cancer screening programmes. Methods: We searched PubMed, OVID Medline, and Embase for all studies published before Nov 1, 2011, that reported prevalence and incidence of anal HPV detection, AIN, and anal cancer in MSM. We calculated summary estimates using random-effects meta-analysis. Findings: 53 studies met the inclusion criteria, including 31 estimates of HPV prevalence, 19 estimates of cytological abnormalities, eight estimates of histological abnormalities, and nine estimates of anal cancer incidence. Data for incident HPV and high-grade AIN were scarce. In HIV-positive men, the pooled prevalence of anal HPV-16 was 35·4% (95% CI 32·9-37·9). In the only published estimate, incidence of anal HPV-16 was 13·0% (9·6-17·6), and clearance occurred in 14·6% (10·2-21·2) of men per year. The pooled prevalence of histological high-grade AIN was 29·1% (22·8-35·4) with incidences of 8·5% (6·9-10·4) and 15·4% (11·8-19·8) per year in two estimates. The pooled anal cancer incidence was 45·9 per 100 000 men (31·2-60·3). In HIV-negative men, the pooled prevalence of anal HPV-16 was 12·5% (9·8-15·4). Incidence of HPV-16 was 11·8% (9·2-14·9) and 5·8% (1·9-13·5) of men per year in two estimates. The pooled prevalence of histological high-grade AIN was 21·5% (13·7-29·3), with incidence of 3·3% (2·2-4·7) and 6·0% (4·2-8·1) per year in two estimates. Anal cancer incidence was 5·1 per 100 000 men (0-11·5; based on two estimates). There were no published estimates of high-grade AIN regression. Interpretation: Anal HPV and anal cancer precursors were very common in MSM. However, on the basis of restricted data, rates of progression to cancer seem to be substantially lower than they are for cervical pre-cancerous lesions. Large, good-quality prospective studies are needed to inform the development of anal cancer screening guidelines for MSM. Funding: Australian Government Department of Health and Ageing. © 2012 Elsevier Ltd.


Bradshaw C.S.,Melbourne Sexual Health Center | Bradshaw C.S.,Monash University | Brotman R.M.,University of Maryland Baltimore County
BMC Infectious Diseases | Year: 2015

Bacterial vaginosis (BV) is one of the great enigmas in women's health, a common condition of unknown aetiology, which is associated with significant morbidity and unacceptably high recurrence rates. While it remains unclear whether BV recurrence is predominantly due to failure of current antibiotic regimens to eradicate BV-associated bacteria (BVAB) and biofilm, a failure of some women to re-establish a resilient Lactobacillus-dominant vaginal microbiota, reinfection from sexual partners, or a combination of these factors, it is inherently challenging to make significant inroads towards this goal. In this review, we will outline why BV is such a clinical and epidemiologic conundrum, and focus on several key approaches that we believe merit discussion and clinical research, including strategies to: i) prevent reinfection (partner treatment trials), ii) boost favourable vaginal Lactobacillus species and promote a Lactobacillus-dominant vaginal microbiome (hormonal contraceptive and probiotic trials) and iii) disrupt vaginal BV-associated biofilm. © 2015 Bradshaw and Brotman.


Lifson A.R.,University of Minnesota | Neuhaus J.,University of Minnesota | Arribas J.R.,Hospital Universitario La Paz | Van Berg-Wolf M.D.,Temple University | And 2 more authors.
American Journal of Public Health | Year: 2010

Objectives. We sought to determine smoklng-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than In the generai population. Methods. For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDSrelated or serious non-AIDS events and overall mortality. Results. Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P<.001), major cardiovascular disease (2.0; P=,002), non-AIDS cancer (1.8; P= .008), and bacterial pneumonia (2.3; P<.001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia. Conclusions. Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care.


Parsons M.S.,University of Melbourne | Loh L.,University of Melbourne | Gooneratne S.,University of Melbourne | Center R.J.,University of Melbourne | And 3 more authors.
AIDS | Year: 2014

Antibody-dependent activation of natural killer (NK) cells might facilitate protective outcomes in the context of HIV exposure or infection. Antibody- dependent activation is heightened in NK cells educated by interactions between killer immunoglobulin-like receptors (KIRs) and their major histocompatibility complex class I ligands during ontogeny. Differentiated NK cells, defined as CD57+, also exhibit enhanced antibody-dependent responsiveness. Although KIRs are more frequently expressed on CD57+ NK cells, the presented data suggest education and differentiation make independent contributions to NK cell anti- HIV envelope antibody-dependent activation. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Ali H.,University of New South Wales | Donovan B.,University of New South Wales | Donovan B.,Sydney Hospital | Wand H.,University of New South Wales | And 7 more authors.
BMJ (Online) | Year: 2013

Objective To measure the effect on genital warts of the national human papillomavirus vaccination programme in Australia, which started in mid-2007. Design Trend analysis of national surveillance data. Setting Data collated from eight sexual health services from 2004 to 2011; the two largest clinics also collected self reported human papillomavirus vaccination status from 2009. Participants Between 2004 and 2011, 85 770 Australian born patients were seen for the first time; 7686 (9.0%) were found to have genital warts. Main outcome measure Rate ratios comparing trends in proportion of new patients diagnosed as having genital warts in the pre-vaccination period (2004 to mid-2007) and vaccination period (mid-2007 to the end of 2011). Results Large declines occurred in the proportions of under 21 year old (92.6%) and 21-30 year old (72.6%) women diagnosed as having genital warts in the vaccination period-from 11.5% in 2007 to 0.85% in 2011 (P<0.001) and from 11.3% in 2007 to 3.1% in 2011 (P<0.001), respectively. No significant decline in wart diagnoses was seen in women over 30 years of age. Significant declines occurred in proportions of under 21 year old (81.8%) and 21-30 year old (51.1%) heterosexual men diagnosed as having genital warts in the vaccination period-from 12.1% in 2007 to 2.2% in 2011 (P<0.001) and from 18.2% in 2007 to 8.9% in 2011 (P<0.001), respectively. No significant decline in genital wart diagnoses was seen in heterosexual men over 30 years of age. In 2011 no genital wart diagnoses were made among 235 women under 21 years of age who reported prior human papillomavirus vaccination. Conclusions The significant declines in the proportion of young women found to have genital warts and the absence of genital warts in vaccinated women in 2011 suggests that the human papillomavirus vaccine has a high efficacy outside of the trial setting. Large declines in diagnoses of genital warts in heterosexual men are probably due to herd immunity.


Zou H.,University of Melbourne | Fairley C.K.,University of Melbourne | Fairley C.K.,Melbourne Sexual Health Center | Guy R.,University of New South Wales | And 2 more authors.
Sexually Transmitted Diseases | Year: 2012

Background: In many countries, the prevalence of bacterial sexually transmitted infections (STIs) among men who have sex with men (MSM) is high. We undertook a systematic review to identify clinic-based strategies for increasing screening and detection of bacterial STIs among MSM. Methods: We reviewed studies that compared screening for or detection of gonorrhea, chlamydia, and syphilis in the presence and the absence of an intervention. The primary end points were STI screening, rescreening, or detection rates. Results: Of 1809 studies identified, 8 fulfilled the inclusion criteria; of these, 4 studies demonstrated significant increases in screening rates for gonorrhea and chlamydia using different strategies (odds ratio range, 1.4-1.9). These included the following: use of a computer alert on an electronic medical record; the introduction of clinic guidelines on STI screening; and short text messaging reminders for repeat STI screening. A further 4 studies demonstrated increases in syphilis testing (odds ratio range, 2.3-21.4), with increased detection of asymptomatic early syphilis in 2 studies. Strategies used included regular serological screening for syphilis during routine human immunodeficiency virus (HIV) care, syphilis serology included with blood tests performed as part of HIV monitoring, use of a computer alert on an electronic medical record, and an electronic medical record system to enhance syphilis retesting after syphilis treatment. Conclusions: A range of interventions has been used, including the application of newer technologies targeting clinicians and patients that appear to be efficacious at increasing screening of MSM for bacterial STIs. Wider application of such interventions could improve STI screening and control in this high-risk population. © 2012 American Sexually Transmitted Diseases Association All rights reserved.


Bissessor M.,Melbourne Sexual Health Center | Fairley C.K.,Melbourne Sexual Health Center | Fairley C.K.,University of Melbourne | Leslie D.,Victorian Infections Diseases Reference Laboratory | And 3 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010

Background: Syphilis continues to be a significant public health problem among HIV-positive men who have sex with men (MSM) internationally. This study aimed to determine whether the routine inclusion of syphilis serology with every blood test performed as part of HIV monitoring increases the detection of early asymptomatic syphilis among HIV-positive MSM. Methods: We examined the effect of this intervention, implemented in January 2007, on the detection of early asymptomatic syphilis among HIV-positive MSM attending the Melbourne Sexual Health Centre, Australia, and compared this with the previous clinic policy of annual syphilis screening. Results: In the 18 months before and after the intervention, the median number of syphilis tests performed per man per year was 1 and 2, respectively. The proportion of MSM diagnosed with early syphilis who were asymptomatic was 21% (3 of 14) and 85% (41 of 48) for the 2 respective periods (P = 0.006). The time between the midpoint since last syphilis serology and diagnosis of syphilis was a median of 107 days (range 9-362) and 45 days (range 23-325) for the 2 periods, respectively (P = 0.018). Conclusions: The inclusion of routine syphilis serology with every blood test performed as part of HIV monitoring in HIV-positive MSM resulted in a large increase in the proportion of men diagnosed with early asymptomatic syphilis. This simple intervention probably also decreased the duration of infectiousness, enhancing syphilis control while also reducing morbidity. © 2010 by Lippincott Williams & Wilkins.


Fairley C.K.,Melbourne Sexual Health Center | Read T.R.H.,Melbourne Sexual Health Center
Current Opinion in Infectious Diseases | Year: 2012

PURPOSE OF REVIEW: This review discusses the vaccines available for the prevention of sexually transmitted infections (STIs), and focuses on the contribution of these vaccines to the control of three infections: hepatitis A, hepatitis B and human papillomavirus (HPV). RECENT FINDINGS: Hepatitis A is an STI in men who have sex with men (MSM). The introduction of the vaccine has resulted in the almost complete disappearance of epidemics of infection despite vaccine coverage of only 30-50% in MSM. In contrast hepatitis B infection sexual transmission both in MSM and heterosexuals continues at low but significant levels despite similar vaccine coverage. The two HPV vaccines are highly effective for the HPV types they contain, and for some related HPV types. Countries using the quadrivalent vaccine have experienced dramatic falls in genital warts in younger women, and to a lesser degree in heterosexual men but not homosexual men. SUMMARY: Vaccines for hepatitis A, B and HPV have been highly effective in controlling STI at a community level. Copyright © Lippincott Williams & Wilkins.


Gooneratne S.L.,University of Melbourne | Richard J.,University of Montréal | Lee W.S.,University of Melbourne | Finzi A.,University of Montréal | And 3 more authors.
Journal of Virology | Year: 2015

Many attempts to design prophylactic human immunodeficiency virus type 1 (HIV-1) vaccines have focused on the induction of neutralizing antibodies (Abs) that block infection by free virions. Despite the focus on viral particles, virus-infected cells, which can be found within mucosal secretions, are more infectious than free virus both in vitro and in vivo. Furthermore, assessment of human transmission couples suggests infected seminal lymphocytes might be responsible for a proportion of HIV-1 transmissions. Although vaccines that induce neutralizing Abs are sought, only some broadly neutralizing Abs efficiently block cell-tocell transmission of HIV-1. As HIV-1 vaccines need to elicit immune responses capable of controlling both free and cell-associated virus, we evaluated the potential of natural killer (NK) cells to respond in an Ab-dependent manner to allogeneic T cells bearing HIV-1 antigens. This study presents data measuring Ab-dependent anti-HIV-1 NK cell responses to primary and transformed allogeneic T-cell targets. We found that NK cells are robustly activated in an anti-HIV-1 Ab-dependent manner against allogeneic targets and that tested target cells are subject to Ab-dependent cytolysis. Furthermore, the educated KIR3DL1+ NK cell subset from HLA-Bw4+ individuals exhibits an activation advantage over the KIR3DL1- subset that contains both NK cells educated through other receptor/ligand combinations and uneducated NK cells. These results are intriguing and important for understanding the regulation of Ab-dependent NK cell responses and are potentially valuable for designing Ab-dependent therapies and/or vaccines. © 2015, American Society for Microbiology.

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