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.

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.

Positivity and Risk Factors for Trichomonas vaginalis Among Women Attending a Sexual Health Clinic in Melbourne, 2006 to 2019.

BACKGROUND: Trichomonas vaginalis is not a notifiable disease in Australia in most states, resulting in limited Australian epidemiological studies. This study aimed to examine the positivity of T. vaginalis in women attending the Melbourne Sexual Health Centre (MSHC) and identify associated factors. METHODS: All women 16 years or older who were tested for T. vaginalis at MSHC from 2006 to 2019 were included. The diagnostic method changed from culture to nucleic acid amplification test in August 2018. The annual positivity of T. vaginalis was calculated. Because of the data completeness, we performed a generalized estimating equations multivariable logistic regression using data from 2011 to 2019 to examine factors associated with T. vaginalis positivity. RESULTS: From 2006 to 2019, 69,739 tests for T. vaginalis were conducted, and 294 tested positive (0.42%; 95% confidence interval [CI], 0.37%-0.47%). Approximately 60% of women tested reported symptoms. After adjusting for potential confounders including the change in diagnostic method, there was a 21% (95% CI, 12%-31%) annual increase in T. vaginalis positivity between 2011 and 2019. Women with concurrent syphilis had the highest odds of testing positive for T. vaginalis (adjusted odds ratio [aOR], 21.55; 95% CI, 6.96-66.78), followed by women who had injected drugs in the last 12 months (aOR, 6.99; 95% CI, 4.11-11.87), were 35 years or older (aOR, 3.47; 95% CI, 2.26-5.35), or had concurrent chlamydia (aOR, 1.77; 95% CI, 1.05-2.99). CONCLUSIONS: The rising positivity of T. vaginalis at MSHC irrespective of change in diagnostic method suggests a concurrent community-wide rise in Melbourne. Given the rising positivity, testing informed by risk factors should be considered.

Clinical Presentation of Incident Syphilis Among Men Who Have Sex with Men Taking HIV Pre-Exposure Prophylaxis in Melbourne, Australia.

BACKGROUND: Current international guidelines on human immunodeficieny virus (HIV) Pre-Exposure Prophylaxis (PrEP) recommend serological screening for syphilis at routine 3-monthly PrEP appointments. The aim of our study was to describe the pattern of clinical presentation of syphilis among men who have sex with men (MSM) taking PrEP. We were interested in whether syphilis is detected through screening at scheduled3-monthly PrEP clinic appointments or whether primary or secondary syphilis presented at unscheduled interval visits. METHODS: This was a retrospective study of MSM attending the PrEP clinic at the Melbourne Sexual Health Centre between February 2016 and March 2019. Serological screening for syphilis was routinely undertaken at 3-monthly PrEP clinic appointments. Diagnoses of early syphilis were identified from PrEP clinic visits and from interim walk-in STI clinic attendances. RESULTS: There were 69 cases of early syphilis among 61 MSM taking PrEP during the study period. There were 24 (35%) primary, 16 (23%) secondary, and 29 (42%) early latent infections. The incidence of early syphilis was 8.6 per 100 person-years. A substantial proportion of primary (58%) and secondary (44%) syphilis diagnoses were made at interim STI clinic attendances, between PrEP appointments. CONCLUSIONS: Syphilis screening at routine 3-monthly PrEP visits alone fails to detect a proportion of primary and secondary syphilis infections and may be insufficient in preventing onward transmission. Education of MSM taking PrEP regarding the risk of syphilis and symptom recognition is necessary together with access to syphilis testing between PrEP visits.

Trends and Risk Factors for Antimicrobial-Resistant Neisseria gonorrhoeae, Melbourne, Australia, 2007 to 2018.

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major public health problem. Traditionally, AMR surveillance programs for N. gonorrhoeae have focused mainly on laboratory data to describe the prevalence and trends of resistance. However, integrating individual-level risk factors (e.g., sexual orientation or international travel) with laboratory data provides important insights into factors promoting the spread of resistant N. gonorrhoeae Here, over a 12-year period, we assessed the trends and risk factors for resistant N. gonorrhoeae in individuals attending a large publicly funded sexual health center in Melbourne, Australia. A total of 7,588 N. gonorrhoeae isolates were cultured from 5,593 individuals between 1 January 2007 and 31 December 2018. The proportion of isolates with penicillin resistance decreased from 49.5% in 2007 to 18.3% in 2018 (ptrend < 0.001) and from 63.5% in 2007 to 21.1% in 2018 for ciprofloxacin resistance (ptrend < 0.001). In contrast, the proportion of isolates displaying decreased susceptibility to ceftriaxone increased from 0.5% in 2007 to 2.9% in 2018 (ptrend < 0.001), with a significant increase in low-level azithromycin resistance, from 2.5% in 2012 to 8.2% in 2018 (ptrend < 0.001). Multivariate analysis identified risk factors for multidrug-resistant (MDR) N. gonorrhoeae, namely, female sex and country of birth, with MDR isolates more common in individuals born in northeast Asia, further highlighting the importance of this region and international travel as factors in the cross-border transmission of MDR N. gonorrhoeae Future surveillance work should incorporate additional epidemiological and genomic data to provide a comprehensive overview of the emergence and spread of resistant N. gonorrhoeae.

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.

Incident HIV infection has fallen rapidly in men who have sex with men in Melbourne, Australia (2013-2017) but not in the newly-arrived Asian-born.

BACKGROUND: We examined differences in incident HIV infection between newly-arrived Asian-born and other men who have sex with men (MSM) after the introduction of universal HIV treatment guidelines in 2015 and pre-exposure prophylaxis in 2016. METHODS: Clinical, demographic, laboratory and behavioural data on MSM presenting for HIV testing at the Melbourne Sexual Health Centre from July 2013 to June 2017 were extracted. We compared the proportion of newly-arrived (four years or less in Australia), Asian-born and other MSM tested each year who were diagnosed with incident HIV infection (negative test within one year or diagnosis with indeterminate or negative Western Blot). RESULTS: We analysed 35,743 testing episodes in 12,180 MSM, including 2781 testing episodes in 1047 newly-arrived Asian-born MSM. The proportion of other MSM tested each year who were diagnosed with incident HIV infection fell from 0.83% in 2014 to 0.38% in 2017 (p = .001), but did not fall in newly-arrived Asian-born MSM (from 1.18% in 2014 to 1.56% in 2017, p = .76). In the multivariate logistic regression, in 2016/2017 but not in 2014/2015, being newly-arrived Asian-born was associated with an increased odds of diagnosis of incident HIV infection (aOR 3.29, 95%CI 1.82-5.94, p < .001). CONCLUSIONS: The epidemiology of HIV in Melbourne Australia has changed dramatically. While there has been an overall reduction amongst MSM, the incidence of HIV in newly-arrived Asian-born MSM remains high. Failing to address these new inequalities leaves individuals at risk and may offset the population benefit of biomedical HIV prevention.

Increased Detection of Pharyngeal and Rectal Gonorrhea in Men Who Have Sex With Men After Transition From Culture To Nucleic Acid Amplification Testing.

BACKGROUND: This before-and-after study measured the impact of a change in testing methods from culture to nucleic acid amplification testing (NAAT) on the detection of pharyngeal and rectal gonorrhea in men who have sex with men (MSM) on a sexual health service level, including the effect on subgroups anticipated to have higher rates of gonorrhea. METHODS: In March 2015, Melbourne Sexual Health Centre changed its laboratory method for gonococcal testing from culture to NAAT using the Aptima Combo 2 and Aptima GC tests. We compared the proportion of tests positive for rectal and pharyngeal gonorrhea in MSM using culture in 2014 with those using NAAT in 2015. RESULTS: The proportion of tests positive for rectal gonorrhea by NAAT was double that obtained by culture (8% vs 3.9%; prevalence ratio [PR], 2.0; 95% confidence interval [CI], 1.8-2.4) and 5-fold for pharyngeal gonorrhea (8.3% vs 1.6%; PR, 5.2; 95% CI, 4.2-6.4). Similar increases in test positivity were observed in human immunodeficiency virus (HIV)-positive and HIV-negative men. By NAAT, test positivity for rectal gonorrhea was higher in HIV-positive compared with HIV-negative men (15.4% vs 7.3%; PR, 2.1; 95% CI, 1.7-2.6). Culture and NAAT had similar test positivity for rectal gonorrhea among men who reported contact with gonorrhea (24.9% vs 25.3%, PR 1.0, 95% CI 0.8-1.4) and men who presented with symptoms of proctitis (22.2% vs 27.9%, PR 1.3, 95% CI 0.8-2.0). CONCLUSIONS: A switch from culture to Aptima Combo 2 testing for extragenital gonorrhea in MSM increased detection and was most marked for pharyngeal infections.

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.

Characteristics of adenovirus urethritis among heterosexual men and men who have sex with men: a review of clinical cases.

BACKGROUND: The aim of this study was to characterise the clinical features of adenovirus urethritis in men and to compare the frequency of these between heterosexual men and men who have sex with men (MSM). METHODS: This was a review of the clinical and laboratory information from men diagnosed with PCR-confirmed adenovirus urethritis at the Melbourne Sexual Health Centre between January 2006 and April 2014. RESULTS: 102 adenovirus urethritis cases were reported, among which 61 were heterosexual men and 41 MSM. Eighty-nine per cent (n=91) had signs of meatitis or conjunctivitis: 51% had meatitis only; 32% meatitis together with conjunctivitis and 6% with conjunctivitis only. The distribution of symptoms and signs was similar among heterosexual men and MSM (p values >0.1). Adenovirus was the sole pathogen found in 93% of cases, excluding gonorrhoea, chlamydia, Mycoplasma genitalium and herpes simplex virus. Only 37% had ≥5 polymorphs per high-power field from a urethral smear. Where samples were still available for adenoviral sequencing (n=20), all were subgroup D. CONCLUSIONS: The clinical features of adenovirus urethritis in men can be distinctive and aid diagnosis, distinguishing it from other treatable causes of male urethritis.

An evaluation of a novel dual treponemal/nontreponemal point-of-care test for syphilis as a tool to distinguish active from past treated infection.

BACKGROUND: Most syphilis point-of-care (POC) tests detect treponemal antibodies, which persist after successful treatment. Subsequent POC tests are positive, despite no active infection, and can lead to unnecessary treatment. We evaluated a new POC test, incorporating a nontreponemal component, to distinguish active from past infection. METHODS: Sera stored at 2 Australian laboratories were tested with DPP Screen and Confirm Assay. Treponemal and nontreponemal test lines were compared to corresponding conventional treponemal and nontreponemal reference test results: immunoassays and rapid plasma reagin (RPR), respectively, with RPR quantification by endpoint titration. POC test outcome concordance with conventional test results was assessed according to serological and clinical categories. RESULTS: Among 1005 serum samples tested, DPP treponemal line sensitivity was 89.8% (95% confidence interval [CI], 87.3%-91.9%) and specificity was 99.3% (95% CI, 97.0%-99.9%). DPP nontreponemal line sensitivity was 94.2% (95% CI, 91.8%-96.0%) and specificity was 62.2% (95% CI, 57.5%-66.6%). DPP test outcome (pair of test lines) was concordant with both reference test results for 94.3% of 404 high-titer infections, 90.1% of 121 low-titer infections, 27.5% of 211 past/treated infections, and 78.1% of 242 infections classified as not syphilis. Among 211 past/treated infections, 49.8% were incorrectly identified as active infection and a further 22.8% as not syphilis. CONCLUSIONS: DPP test use would result in identification of >93% of active syphilis infections, whereas just over half of past infections would be diagnosed as past or not syphilis, avoiding unnecessary treatment compared with other POC tests. This may be at the expense of missing some active infections; thus, its potential benefits will depend on the prevalence of past vs active infection in a population.

Substantial increases in chlamydia and gonorrhea positivity unexplained by changes in individual-level sexual behaviors among men who have sex with men in an Australian sexual health service from 2007 to 2013.

BACKGROUND: To determine the risk-adjusted temporal trend of gonorrhea and chlamydia positivity and associated risk behaviors among men who have sex with men (MSM) attending a sexual health clinic in Melbourne in Australia. METHODS: Gonorrhea and chlamydia positivity by anatomical site adjusted for year of test, age, number of sexual partners, and condom use among MSM attending Melbourne Sexual Health Centre from 2007 to 2013 were calculated using generalized estimating equation regression models. RESULTS: A total of 12,873 MSM were included with a median age of 30.0 years. The proportion with pharyngeal, urethral, and anal gonorrhea was 1.7%, 2.3%, and 2.9%, respectively. The adjusted odds of gonorrhea positivity increased by 9% (95% confidence interval [CI], 3%-15%), 11% (95% CI, 6%-17%), and 12% (95% CI, 7%-17%) per year, respectively. The proportion of MSM who were infected with anal chlamydia was 5.6%, with an average increase of 6% (95% CI, 3%-10%) per year; however, no significant change was observed in urethral chlamydia positivity (adjusted odds ratio, 1.02; 95% CI, 0.98-1.06). Increases in gonorrhea and chlamydia positivity were primarily restricted to MSM who reported more than 10 partners in 12 months. The number of partners in the last 12 months fell from 16.6 to 10.5, whereas consistent condom use with casual partners decreased from 64.6% to 58.9% over the study period. CONCLUSIONS: Gonorrhea and chlamydia have increased among MSM despite the decrease in the number of sexual partners and are occurring primarily in MSM with high numbers of partners and persist after adjusting for known risk factors, suggesting that unmeasured factors (e.g., more assortative mixing patterns) may explain the observed changes.

Gonorrhoea notifications and nucleic acid amplification testing in a very low-prevalence Australian female population.

OBJECTIVES: To examine whether the rapid increase of gonorrhoea notifications in Victoria, Australia, identified by nucleic acid amplification test (NAAT) is supported by similar changes in diagnoses by culture, which has higher specificity, and to determine the proportion of tests positive among women tested. DESIGN, SETTING AND PARTICIPANTS: Retrospective analysis of Medicare reporting of dual NAATs in Victoria, Victorian Department of Health gonorrhoea notifications, and gonorrhoea culture data at the Melbourne Sexual Health Centre (MSHC), among women, 2008 to 2013. MAIN OUTCOME MEASURES: Gonorrhoea notifications and testing methods. RESULTS: Gonorrhoea cases identified by NAAT increased from 98 to 343 cases over the study period. Notifications by culture alone decreased from 19 to five cases. The proportion of NAATs positive for gonorrhoea in Victoria was low (0.2%-0.3%) and did not change over time (P for trend, 0.66). Similarly, the proportion of women tested at the MSHC for gonorrhoea who tested positive (0.4%-0.6%) did not change over time (P for trend, 0.70). Of untreated women who had a positive NAAT result for gonorrhoea and were referred to the MSHC, 10/25 were confirmed by culture. CONCLUSIONS: The positivity of gonorrhoea in women identified by culture remains stable over time. Using NAAT for gonorrhoea screening in low-prevalence populations will result in many false positives. Positive NAAT results among low-risk women should be regarded as doubtful, and confirmatory cultures should be performed.

High prevalence of rectal gonorrhoea among men reporting contact with men with gonorrhoea: Implications for epidemiological treatment.

BACKGROUND: This study aimed to determine the prevalence of gonorrhoea and factors associated with rectal gonorrhoea among men reporting sexual contact with men with gonorrhoea. METHODS: Men who presented to Melbourne Sexual Health Centre reporting sexual contact with a male with gonorrhoea were prospectively identified between March 2011 and December 2013. These men were screened for pharyngeal and rectal gonorrhoea using culture. The prevalence of gonorrhoea among contacts was compared to that among all men who have sex with men (MSM) screened at the clinic over the same period. RESULTS: Among 363 contacts of gonorrhoea the prevalence of rectal gonorrhoea was 26.4% (95% CI: 21.8%-31.0%) compared to 3.9% (95% CI: 3.7%-4.2%) among clinic attendees (p < 0.001). The prevalence of pharyngeal gonorrhoea among contacts was 9.4% (95% CI: 6.4%-12.4%) compared to 2.1% (95% CI: 1.9%-2.4%) among clinic attendees (p < 0.001). Among contacts who reported not always using condoms during receptive anal sex with casual partners, rectal gonorrhoea was cultured in 42.4% compared with 12.7% among contacts reporting no receptive anal sex (p < 0.001) and 20.2% among those reporting always using condoms (p < 0.001). On multivariate analysis rectal gonorrhoea was associated with inconsistent condom use during receptive anal sex with casual partners (adjusted odds ratio (AOR): 4.16; 95% CI: 1.87-9.26) and a reported past history of gonorrhoea (AOR: 1.77; 95% CI: 1.01-3.14). CONCLUSIONS: The high proportion of positive cases of gonorrhoea among contacts in this study supports epidemiological treatment of MSM presenting as contacts of gonorrhoea.

The etiology of infectious proctitis in men who have sex with men differs according to HIV status.

We compared the spectrum of pathogens responsible for infectious proctitis between HIV-positive and HIV-negative men who have sex with men. Only 32% of men with herpes simplex virus (HSV)-associated proctitis had visible external anal ulceration.The etiology of infectious proctitis among HIV-positive and HIV-negative men is as follows: chlamydia (23.4% vs. 21.7%, P = 0.7), gonorrhea (13.4% vs. 10.8%, P = 0.5), HSV-1 (14.2% vs. 6.5%, P = 0.04), HSV-2 (22% vs. 12.3%, P = 0.03), lymphogranuloma venereum (7.8% vs. 0.7%, P = 0.004), and multiple infections (17.7% vs. 8.6%, P = 0.017). Thirty-two percent with HSV proctitis had external anal ulceration.

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.

Directly Sequenced Genomes of Contemporary Strains of Syphilis Reveal Recombination-Driven Diversity in Genes Encoding Predicted Surface-Exposed Antigens.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), remains an important public health problem with an increasing worldwide prevalence. Despite recent advances in in vitro cultivation, genetic variability of this pathogen during infection is poorly understood. Here, we present contemporary and geographically diverse complete treponemal genome sequences isolated directly from patients using a methyl-directed enrichment prior to sequencing. This approach reveals that approximately 50% of the genetic diversity found in TPA is driven by inter- and/or intra-strain recombination events, particularly in strains belonging to one of the defined genetic groups of syphilis treponemes: Nichols-like strains. Recombinant loci were found to encode putative outer-membrane proteins and the recombination variability was almost exclusively found in regions predicted to be at the host-pathogen interface. Genetic recombination has been considered to be a rare event in treponemes, yet our study unexpectedly showed that it occurs at a significant level and may have important impacts in the biology of this pathogen, especially as these events occur primarily in the outer membrane proteins. This study reveals the existence of strains with different repertoires of surface-exposed antigens circulating in the current human population, which should be taken into account during syphilis vaccine development.

Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016.

AIM: Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016. OBJECTIVES: We examined the time from HIV infection to virological suppression in MSM who were first diagnosed at Melbourne Sexual Health Centre between 2007 and 2016. DESIGN: Retrospective cohort. METHODS: Date of infection was imputed from the testing history or serological evidence of recent infection (negative or indeterminate western blot) or baseline CD4 cell count. Date of virological suppression was determined using clinical viral load data. We analysed predictors of diagnosis with serological evidence of recent infection (logistic regression) and time from diagnosis to suppression and from infection to suppression (Cox regression) using demographic, clinical, and behavioral covariates. RESULTS: Between 2007 and 2016, the median time from HIV infection to diagnosis fell from 6.8 to 4.3 months (P = 0.001), from diagnosis to suppression fell from 22.7 to 3.2 months (P < 0.0001), and from infection to suppression fell from 49.0 to 9.6 months (P < 0.0001). Serological evidence of recent infection increased from 15.6 to 34.3% (P < 0.0001) of diagnoses. In the multivariate analyses, age, being recently arrived from a non-English speaking country, history of IDU, other sexually transmitted infections, and sexual risk were not associated with any of these measures. CONCLUSION: The duration of infectiousness in MSM diagnosed with HIV infection at Melbourne Sexual Health Centre in Victoria has fallen dramatically between 2007 and 2016 and the proportion diagnosed with serological evidence of recent infection has increased. This effect is observed across all population subgroups and marks a positive milestone for the treatment as prevention paradigm.