Management of acute sexual assault presenting to a large Australian sexual health clinic in 2012-2021: a retrospective clinical audit.

Background The incidence of sexual assault continues to rise in Australia. This study aimed to describe the nature of assault, HIV/STI positivity, and its management at a sexual health clinic. Methods We performed a chart review of 516 sexual assault cases presenting to Melbourne Sexual Health Centre between 2012 and 2021, collecting data on victim demographics, details of assault, HIV/STI testing and positivity, police involvement, and offer of counselling. Results We included 516 cases: 124 males (24.0%); 384 females (74.4%); and eight transgender (1.6%) victims. The proportion of assault cases presenting to Melbourne Sexual Health Centre increased from 0.1% (37/37,070) in 2012 to 0.2% (56/36,514) in 2021 (P trend =0.006). HIV post-exposure prophylaxis was prescribed for 64.5% (80/124) of males and 12.5% (48/384) of females. Among victims, 69.4% (358/516) were tested for HIV and no one tested positive, while 71.9% (371/516) were tested for syphilis, with 1.6% (6/371) positive. Gonorrhoea and chlamydia were tested at the oropharynx (44.8% [231/516] vs 28.7% [148/516]), genitals (83.7% [432/516] vs 92.4% [477/516]) and anorectum (35.3% [182/516] vs 35.3% [182/516]). Positivity for gonorrhoea and chlamydia were: 2.6% (6/231) vs 2.0% (3/148) at oropharynx, 1.4% (6/432) vs 2.9% (14/477) at genitals, and 5.5% (10/182) vs 7.1% (13/182) at anorectum. According to clinical records, 25.2% (130/516) of victims sought police involvement, and 71.7% (370/516) were offered counselling. Conclusions Sexual assault was an uncommon presentation at Melbourne Sexual Health Centre, with diverse circumstances surrounding assault; however, clinical documentation varied, indicating a need for a standard primary care protocol for clients presenting with acute sexual assault.

Rapid detection of monkeypox virus using a CRISPR-Cas12a mediated assay: a laboratory validation and evaluation study.

BACKGROUND: The 2022 outbreak of mpox (formerly known as monkeypox) led to the spread of monkeypox virus (MPXV) in over 110 countries, demanding effective disease management and surveillance. As current diagnostics rely largely on centralised laboratory testing, our objective was to develop a simple rapid point-of-care assay to detect MPXV in clinical samples using isothermal amplification coupled with CRISPR and CRISPR-associated protein (Cas) technology. METHODS: In this proof-of-concept study, we developed a portable isothermal amplification CRISPR-Cas12a-based assay for the detection of MPXV. We designed a panel of 22 primer-guide RNA sets using pangenome and gene-agnostic approaches, and subsequently shortlisted the three sets producing the strongest signals for evaluation of analytical sensitivity and specificity using a fluorescence-based readout. The set displaying 100% specificity and the lowest limit of detection (LOD) was selected for further assay validation using both a fluorescence-based and lateral-flow readout. Assay specificity was confirmed using a panel of viral and bacterial pathogens. Finally, we did a blind concordance study on genomic DNA extracted from 185 clinical samples, comparing assay results with a gold-standard quantitative PCR (qPCR) assay. We identified the optimal time to detection and analysed the performance of the assay relative to qPCR using receiver operating characteristic (ROC) curves. We also assessed the compatibility with lateral-flow strips, both visually and computationally, where strips were interpreted blinded to the fluorescence results on the basis of the presence or absence of test bands. FINDINGS: With an optimal run duration of approximately 45 min from isothermal amplification to CRISPR-assay readout, the MPXV recombinase polymerase amplification CRISPR-Cas12a-based assay with the selected primer-guide set had an LOD of 1 copy per µL and 100% specificity against tested viral pathogens. Blinded concordance testing of 185 clinical samples resulted in 100% sensitivity (95% CI 89·3-100) and 99·3% specificity (95% CI 95·7-100) using the fluorescence readout. For optimal time to detection by fluorescence readout, we estimated the areas under the ROC curve to be 0·98 at 2 min and 0·99 at 4 min. Lateral-flow strips had 100% sensitivity (89·3-100) and 98·6% specificity (94·7-100) with both visual and computational assessment. Overall, lateral-flow results were highly concordant with fluorescence-based readouts (179 of 185 tests, 96·8% concordant), with discrepancies associated with low viral load samples. INTERPRETATION: Our assay for the diagnosis of mpox displayed good performance characteristics compared with qPCR. Although optimisation of the assay will be required before deployment, its usability and versatility present a potential solution to MPXV detection in low-resource and remote settings, as well as a means of community-based, on-site testing. FUNDING: Victorian Medical Research Accelerator Fund and the Australian Government Department of Health.

Treponema pallidum Detection at Asymptomatic Oral, Anal, and Vaginal Sites in Adults Reporting Sexual Contact with Persons with Syphilis.

We investigated Treponema pallidum PCR positivity at mucosal sites (oral, anal, and vaginal sites) among adults who had sexual contact with a person with syphilis (syphilis contacts). All syphilis contacts had oral rinse and swab samples collected for testing. Men who have sex with men had anal swab and women had vaginal swab samples collected for testing, regardless of the presence of lesions. Of 407 persons tested, 42 (10%) had early syphilis diagnosed; of those, 19 (45%) tested positive by PCR from any anatomic site and had a positive serologic test. T. pallidum was positive from vaginal samples in 3 women, anal samples in 3 men, and oral cavity samples in 2 women and 3 men, without symptoms at those sites. Three women had no prior syphilis serologic test. T. pallidum detection at asymptomatic mucosal sites suggests early syphilis infections, particularly in cases that would conventionally be staged as latent syphilis of unknown duration.

The role of syphilis self-testing as an additional syphilis testing approach in key populations: a systematic review and meta-analysis.

BACKGROUND: Syphilis is causing epidemics in many countries. Syphilis self-testing (SST) has potential to increase testing and treatment coverage in the same manner as documented for self-testing of, for example, HIV, hepatitis C virus, and COVID-19. We aimed to synthesise current evidence on the utility of SST. METHODS: We conducted a systematic review and, where possible, meta-analysis. We searched MEDLINE, Embase, CINAHL, Scopus, and Web of Science for publications published from Jan 1, 2000, to Oct 13, 2022. We included publications with original data on any syphilis rapid tests, including dual HIV-syphilis tests. Study populations were not restricted. We used random-effects meta-analysis to calculate the pooled proportion of people offered SST who undertook the test. The systematic review was registered in PROSPERO (CRD42022302129). FINDINGS: In total, 40 499 citations were identified. 11 publications from seven studies from the USA, Zimbabwe, and China met eligibility criteria. Of those, four studies reported data from men who have sex with men and five studies used dual HIV-SST. Using data from one randomised controlled trial and three observational studies, the pooled proportion of people who received SST kits who undertook the test was 88% (95% CI 85-91). No studies provided data on the sensitivity or specificity of SST. Overall, user and provider preference for SST was high, with participants reporting convenience, privacy, rapid results, autonomy, trust in blood-based tests, decreased facility contact, and time savings, with individuals being able to correctly self-test. Publications from China reported that SST had lower costs per person tested than existing facility-based testing options. INTERPRETATION: Our review builds on the literature for self-testing across different disease areas and demonstrates that SST has the potential to reach underserved populations. As this review found that SST use was acceptable and feasible to implement, SST can be used as an additional syphilis testing approach. Since no data on the sensitivity and specificity of SST were found, further implementation research will be required to guide the best strategies for SST service delivery and future scale-up. FUNDING: WHO, Australian National Health and Medical Research Council, and Unitaid.

Mpox knowledge, vaccination and intention to reduce sexual risk practices among men who have sex with men and transgender people in response to the 2022 mpox outbreak: a cross-sectional study in Victoria, Australia.

BACKGROUND: The first mpox case was reported in May 2022 in Australia. Most cases have been diagnosed in men who have sex with men (MSM). This study aimed to examine community understanding of mpox, attitudes towards vaccination, and potential changes in sexual practices surrounding the mpox outbreak among MSM and transgender people in Victoria, Australia. METHODS: Participants were recruited from sexual health clinics and communities in Victoria, Australia, in August-October 2022. Participants were asked about their understanding and knowledge of mpox, vaccination uptake and intentions to change sexual practices. Univariable and multivariable logistic regression was performed to examine the factors associated with mpox vaccine uptake. RESULTS: Most participants (97.8%, 525/537) had heard about mpox and 10.5% (55/525) knew someone who had had mpox. Of the 12 mpox knowledge questions, the median score of correct answers was 10 (IQR=8-11) out of a maximum of 12. More than a third (36.6%, 191/522) had been vaccinated against mpox. MSM who had a good knowledge of mpox had the highest odds of receiving mpox vaccine compared with those who had poor knowledge (aOR=4.05; 95% CI: 1.54-10.61). To prevent mpox, half reported they would reduce having sex with casual partners, stop having chemsex (used drugs for the purpose of sex), stop attending sex-on-premises-venues, and stop having group sex. A quarter reported they would increase condom use for anal sex. CONCLUSIONS: One-third of high-risk participants and a substantial proportion of participants intended to reduce or stop certain practices, which may explain the large reduction in mpox cases.

Clinical and laboratory aspects of condylomata lata lesions of syphilis.

OBJECTIVES: Condylomata lata are a less common but distinctive syphilitic lesion. Variable theories as to their nature and origin exist. The aim of this study was to determine the clinical and laboratory characteristics of condylomata lata by determining (1): the most closely aligned stage of syphilis, based on the rapid plasma reagin (RPR) titre; (2) symptom duration and (3) Treponema pallidum PCR cycle threshold (CT) values, as an indicator of organism load. METHODS: This was a retrospective study of patients with T. pallidum PCR-positive condylomata lata lesions, attending a clinic in Melbourne, Australia, between 2011 and 2021. Syphilis serology was undertaken and RPR titres compared between condylomata lata, primary and secondary syphilis cases. RESULTS: 51 cases with T. pallidum PCR-positive condylomata lata were included. 41 cases were in men, 40 of whom were men who have sex with men (MSM), and 10 in women. Twelve of 51 (24%) cases were in HIV-positive MSM. Thirty-three of 51 (65%) had other mucocutaneous signs of secondary syphilis; 18 (35%) had no other signs of secondary syphilis. The median RPR titre among the 51 condylomata lata cases was 1:128, compared with the median RPR titre of primary syphilis (1:4) and of secondary syphilis (1:128). The median duration of lesions was 24 (IQR 10-60) days, with no significant difference between those with and without other signs of secondary syphilis (p=0.75). Median CT values for condylomata lata (CT=31) and primary syphilis (CT=31) were significantly lower than for other secondary syphilis lesion types (CT=33), indicating higher T. pallidum loads for condylomata lata and primary lesions compared with other secondary syphilis lesion types. DISCUSSION: These findings support condylomata lata as lesions that occur during the secondary stage of syphilis and which are likely to be highly infectious.

Anal and oral detection of Treponema pallidum in men who have sex with men with early syphilis infection.

OBJECTIVES: We aimed to characterise patterns of anal and oral detection of Treponema pallidum among men who have sex with men (MSM) with early syphilis. METHODS: 200 MSM with serologically confirmed primary, secondary and early latent syphilis were tested with T. pallidum polA PCR using an anal canal swab, oral rinse, plus swabs from any anal and oral lesions in a prospective, cross-sectional study. Anal and oral T. pallidum cycle threshold values were compared between subsets of men and according to rapid plasma reagin (RPR) titre. RESULTS: Of 200 men with early syphilis, 45 and 48 had anal and oral T. pallidum detected, respectively. Cycle threshold values were lower with anal compared with oral T. pallidum whether lesions were present or not. Among 27 and 42 men with anal and oral T. pallidum detected, respectively, and no anal or oral primary lesion, frequency of detection increased with increasing RPR titre, with 95% (25/27) and 98% (41/42) of shedding from respective sites occurring with RPR titres ≥1:16. 6.5% (13/200) of men with syphilis had concurrent detection of T. pallidum from both anal and oral sites: 9/13 with secondary syphilis, 7/9 of whom had anal lesions with a median duration of 30 days (range 7-180 days). CONCLUSIONS: These data suggest T. pallidum load at the anus is higher than at the oral cavity and that a subset of men with secondary syphilis and prolonged anal lesions may be relatively infectious. Earlier detection and treatment of syphilis, when RPR titres are lower than 1:16, could potentially reduce infectiousness from anal and oral sites.

Timing of primary syphilis treatment and impact on the development of treponemal antibodies: a cross-sectional clinic-based study.

BACKGROUND: Serology is negative in a proportion of primary syphilis cases where Treponema pallidum PCR testing is positive. We aimed to identify discordant, T. pallidum PCR-positive, serology-negative primary syphilis cases and any clinical or laboratory factors associated with failure to subsequently seroconvert. METHODS: Serodiscordant primary syphilis cases that were T. pallidum PCR-positive and serology-negative (including rapid plasma reagin, T. pallidum particle agglutination, T. pallidum enzyme immunoassay or T. pallidum chemiluminescence assay) were identified from the Melbourne Sexual Health Centre electronic records between April 2011 and December 2019. Clinical and laboratory associations were examined. RESULTS: There were 814 primary syphilis cases in the study period and 38 (4.7%) were serodiscordant, 35 in men who have sex with men. Thirty-two had follow-up serology performed a median of 24 days later, of which 16 (50%) seroconverted, mostly (81%) within 6 weeks. Failure to seroconvert was significantly associated with treatment on day 1. Of the 12 cases treated on day 1, 10 (83%) failed to seroconvert compared with 6 of 20 (30%) among those who were treated after day 1. DISCUSSION: Earlier treatment of primary syphilis can prevent the development of serological markers. T. pallidum PCR can identify primary syphilis lesions before the development of serological markers and improve diagnosis of early primary syphilis lesions. Serology alone will miss a proportion of primary syphilis infections and should be repeated if a diagnosis of syphilis is being considered.

Treponema pallidum detection in lesion and non-lesion sites in men who have sex with men with early syphilis: a prospective, cross-sectional study.

BACKGROUND: Syphilis transmission is increasing, and precisely how Treponema pallidum is transmitted sexually from person to person is unclear. We aimed to determine the frequency of T pallidum shedding from potentially asymptomatic sites and the stage of infection at which shedding is most frequent in men who have sex with men (MSM), who have been disproportionately affected by syphilis. METHODS: We did a prospective, cross-sectional study in MSM recruited from Melbourne Sexual Health Centre (Melbourne, VIC, Australia). Men were eligible if they were aged 18 years or older, reported sex with men during the past 12 months, and had laboratory confirmed primary, secondary, or early latent syphilis, consistent with Australian definitions. Primary and secondary syphilis lesions were swabbed and non-lesion samples were collected via oral rinse, oral cavity swab, anal canal swab, urine, and semen. Samples were tested for T pallidum using PCR assays targeting polA (lesion and non-lesion samples) and 47 kDa (non-lesion samples only) gene targets. The primary outcome was the proportion of men with T pallidum detected from potentially asymptomatic sites-namely, the mouth, anus, urethra, and semen. FINDINGS: Between Nov 30, 2015, and May 23, 2019, 246 MSM were screened for inclusion, of whom 200 had serologically confirmed early syphilis and were included in the study: 54 (27%) of 200 had primary syphilis, 93 (47%) had secondary syphilis, and 53 (27%) had early latent syphilis. T pallidum DNA was detected in 48 (24%; 95% CI 18·3-30·5) of 200 men by oral rinse or oral lesion swab, or both, of whom 24 had no oral lesions. Oral T pallidum detection was most frequent in those with secondary syphilis compared with those at other stages of disease (41 [44%] of 93 vs seven [7%] of 107; p<0·0001), and in men with rapid plasma reagin titres of 1/64 or higher compared with those with lower titres (37 [32%] of 117 vs 11 [13%] of 83; p=0·0026). T pallidum was detected by anal canal swab or anal lesion swab, or both, in 45 (23·0%; 95% CI 17·3-29·5) of 196 men with available samples, of whom ten had no anal lesion. Furthermore, T pallidum was detected in urine samples of 12 (6·1%, 3·2-10·3) of 198 men and in semen samples from six (12·0%, 4·5-24·3) of 50 men who provided samples. Among the 93 men with secondary syphilis, 69 (74%) had T pallidum detected at any site, and 24 (26%) had detection at two or more separate sites. Among the 54 men with primary syphilis, 49 (91%) had T pallidum detected at any site, and 11 (20%) had detection at two or more separate sites. Among the 53 men with early latent syphilis, four (8%) had T pallidum detected at any site and none had T pallidum detected at two or more separate sites. INTERPRETATION: Unrecognised oral and anal shedding of T pallidum occurs in MSM with early syphilis, most frequently in those with secondary syphilis, suggesting secondary syphilis is the most infectious stage and that earlier detection and treatment of syphilis to prevent progression to the secondary stage might improve syphilis control. Future research is needed to ascertain the contribution of shedding of T pallidum from non-lesion sites to transmission of syphilis. FUNDING: Australian National Health and Medical Research Council.

Access to sexual health services after the rapid roll out of the launch of pre-exposure prophylaxis for HIV in Melbourne, Australia: a retrospective cross-sectional analysis.

Background On 26 July 2016, Victoria began a large study of HIV pre-exposure prophylaxis, called PrEPX, that involved the creation of around 2600 appointments over 3 months across multiple sites in Melbourne, Australia. At this time, the Melbourne Sexual Health Centre (MSHC) appeared to have a larger demand on its services. The aim of the present study was to determine whether this apparent increase in demand was substantially different from other demand fluctuations. METHODS: Patients presenting to the MSHC from 2014 to 2016 were reviewed. Demographic characteristics, sexual risks and sexually transmitted infection diagnoses were extracted from the clinical database. RESULTS: There were 115522 walk-in presentations for care and a rise in presentations in the week following the launch of the PrEPX study, but at least six similar peaks occurred that year. The peak coinciding with the launch of PrEPX was only apparent for men who have sex with men. There was a substantial increase in the proportion of patients who could not be seen (i.e. triaged out), from 10% in the week before PrEPX to 22.2% in the second week after, but this was primarily due to staff absences. At the time of the PrEPX study, data were collected on the duration of symptoms for common conditions and found no significant (P>0.29) change in the average duration of symptoms compared with that seen before the PrEPX launch. CONCLUSIONS: The increase in the number of medical consultations required for the PrEPX study did not result in excessive demand for public sexual health services.

Clinical factors associated with syphilis concordance in men in sexual partnerships: a cross-sectional couples study.

BACKGROUND: Syphilis infections continue to increase among men who have sex with men (MSM) in many countries, with rates often higher among HIV-positive MSM. There is limited understanding of the risk and determinants of syphilis transmission between men. We aimed to examine the concordance of early syphilis infection between male sexual partners and clinical factors associated with transmission. METHODS: Men attending Melbourne Sexual Health Centre with their male partners, where at least one was diagnosed with early syphilis, were identified from linkage of partner records between March 2011 and April 2016. Early latent syphilis was defined as a new asymptomatic syphilis presentation of less than 2 years' duration. Associations between concordance and potential risk factors were examined using Fisher's exact test. RESULTS: Among 43 couples (86 men) identified, there were 13 couples (26 men) where both were diagnosed with early syphilis, representing a concordance rate of 30.2% (95% CI 17.2% to 46.1%). Among the 13 concordant couples, 5 men had primary syphilis (4 penile, 1 anal), 11 secondary syphilis (8 generalised rash, 3 penile, 2 anal, 1 oral lesion) and 10 early latent infections. Concordance was higher among couples where at least one partner had secondary syphilis compared with couples where neither partner had secondary syphilis (53% (9/17) vs 15% (4/26), P=0.016). Furthermore, concordance was higher among couples where one was HIV positive compared with couples where both were HIV negative (62% (5/8) vs 23% (8/35), P=0.042). CONCLUSIONS: There was an overall concordance rate of 30%. Higher concordance rates for early syphilis infection between male sexual partners were associated with HIV and secondary syphilis.

Dolutegravir with tenofovir disoproxil fumarate-emtricitabine as HIV postexposure prophylaxis in gay and bisexual men.

OBJECTIVES: Completion rates for HIV postexposure prophylaxis (PEP) are often low. We investigated the adherence and safety of dolutegravir (DTG; 50 mg daily) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC; 300/200 mg, respectively) as three-drug PEP in gay and bisexual men. DESIGN: Open-label, single-arm study at three sexual health clinics and two emergency departments in Australia. METHODS: In total, 100 HIV-uninfected gay and bisexual men requiring PEP received DTG and TDF-FTC for 28 days. The primary end point was PEP failure (premature PEP cessation or primary HIV infection through week 12). Additional end points were adherence by self-report (n = 98) and pill count (n = 55), safety, and plasma drug levels at day 28. RESULTS: PEP completion was 90% (95% confidence interval 84-96%). Failures (occurring at a median 9 days, interquartile range 3-16) comprised loss to follow-up (9%) and adverse event resulting in study drug discontinuation (headache, 1%). No participant was found to acquire HIV through week 12. Adherence to PEP was 98% by self-report and in the 55 participants with corresponding pill count data. The most common clinical adverse events were fatigue (26%), nausea (25%), diarrhoea (21%), and headache (10%). There were only four grade 3-4 subjective adverse events. The most common laboratory adverse event was raised alanine aminotransferase (22%), but there was no case of clinical hepatitis. At day 28, the mean estimated glomerular filtration rate decrease was 14 ml/min/1.73m (SD 17, P = 0.001); an estimated glomerular filtration rate of less than 60 ml/min/1.73m occurred in 3%. CONCLUSIONS: DTG with TDF-FTC is a well tolerated option for once-daily PEP.

Painful and multiple anogenital lesions are common in men with Treponema pallidum PCR-positive primary syphilis without herpes simplex virus coinfection: a cross-sectional clinic-based study.

BACKGROUND: Chancres, the hallmark of primary syphilis, are classically described as single, painless ulcers at the site of Treponema pallidum inoculation. We aimed to determine the frequency of painful or multiple anogenital lesions of primary syphilis among men, whether there was concurrent herpes simplex virus (HSV) infection and whether HIV status altered clinical presentations. METHODS: This study was conducted among men with T. pallidum PCR-positive lesions, attending a clinic in Melbourne, Australia, between 2009 and 2014. Lesions were also tested with HSV PCR, and syphilis serology undertaken. RESULTS: 183 men with T. pallidum PCR-positive primary anogenital lesions were included. 89% were men who have sex with men, and 10.9% were heterosexual. 38 men (20.8%) were HIV positive. Anal lesions were more common in HIV-positive men (34.2%) than in HIV-negative men (11.6%). Primary lesions were frequently painful (49.2%) or multiple (37.7%), and infrequently associated with HSV (2.7%). Of 37 men with both painful and multiple primary lesions, only 8% had concurrent HSV. Presentation was not significantly altered by HIV status. CONCLUSIONS: Primary syphilis lesions are often painful and/or multiple in the absence of herpes coinfection, and may be clinically misdiagnosed.