Sexual behaviour and incidence of sexually transmitted infections among men who have sex with men (MSM) using daily and event-driven pre-exposure prophylaxis (PrEP): Four-year follow-up of the Amsterdam PrEP (AMPrEP) demonstration project cohort.

BACKGROUND: An increasing number of countries are currently implementing or scaling-up HIV pre-exposure prophylaxis (PrEP) care. With the introduction of PrEP, there was apprehension that condom use would decline and sexually transmitted infections (STIs) would increase. To inform sexual health counselling and STI screening programmes, we aimed to study sexual behaviour and STI incidence among men who have sex with men (MSM) and transgender women who use long-term daily or event-driven PrEP. METHODS AND FINDINGS: The Amsterdam PrEP demonstration project (AMPrEP) was a prospective, closed cohort study, providing oral daily PrEP and event-driven PrEP to MSM and transgender women from 2015 to 2020. Participants could choose their PrEP regimen and could switch at each three-monthly visit. STI testing occurred at and, upon request, in-between 3-monthly study visits. We assessed changes in numbers of sex partners and condomless anal sex (CAS) acts with casual partners over time using negative binomial regression, adjusted for age. We assessed HIV incidence and changes in incidence rates (IRs) of any STI (i.e., chlamydia, gonorrhoea, or infectious syphilis) and individual STIs over time using Poisson regression, adjusted for age and testing frequency. A total of 367 participants (365 MSM) commenced PrEP and were followed for a median 3.9 years (interquartile range [IQR] = 3.4-4.0). Median age was 40 years (IQR = 32-48), 315 participants (85.8%) self-declared ethnicity as white and 280 (76.3%) had a university or university of applied sciences degree. Overall median number of sex partners (past 3 months) was 13 (IQR = 6-26) and decreased per additional year on PrEP (adjusted rate ratio [aRR] = 0.86/year, 95% confidence interval [CI] = 0.83-0.88). Overall median number of CAS acts with casual partners (past 3 months) was 10 (IQR = 3-20.5) and also decreased (aRR = 0.92/year, 95% CI = 0.88-0.97). We diagnosed any STI in 1,092 consultations during 1,258 person years, resulting in an IR of 87/100 person years (95% CI = 82-92). IRs of any STI did not increase over time for daily PrEP or event-driven PrEP users. Two daily PrEP users, and no event-driven PrEP users, were diagnosed with HIV during their first year on PrEP. Study limitations include censoring follow-up due to COVID-19 measures and an underrepresentation of younger, non-white, practically educated, and transgender individuals. CONCLUSIONS: In this prospective cohort with a comparatively long follow-up period of 4 years, we observed very low HIV incidence and decreases in the numbers of casual sex partners and CAS acts over time. Although the STI incidence was high, it did not increase over time. TRIAL REGISTRATION: The study was registered at the Netherlands Trial Register (NL5413) https://www.onderzoekmetmensen.nl/en/trial/22706.

Sexual Distancing During 5 Periods Around and During the COVID-19 Pandemic, Amsterdam, the Netherlands.

BACKGROUND: Social and sexual distancing (ie, abstaining from sex with persons outside one's household) was important in the control of the COVID-19 pandemic. Compliance to distancing measures can change over time. We assessed changes in compliance to the sexual distancing measures during five periods of the COVID-19 pandemic in the Netherlands. METHODS: Between November 2021 and March 2022, we used a structured questionnaire containing questions about sexual behavior and factors that could have influenced compliance with sexual distancing. Variables related to sexual behavior were measured for 5 periods, before and during the pandemic, delineated by imposement and relaxation of lockdown measures. RESULTS: Eight hundred seventy participants (predominantly MSM) completed the questionnaire. We found that compliance to the sexual distancing measures decreased over time. The number of casual partners was highest after the lockdown measures were relaxed for the second time (April 2021 to March 2022), and even higher than before the first lockdown. Factors positively associated with sexual distancing compliance were: having confidence in the information provided by the government and experiencing less or similar need for physical contact compared with before the pandemic. Factors that lowered compliance over time were: previously having had COVID-19, perceiving the lockdown measures as overstated, having sex with casual partners and similar drug use during the pandemic as before. CONCLUSIONS: Our findings suggest that sexual distancing measures are difficult to maintain for a long period. Other measures, such as confinement to a small network of known partners, might be more effective for longer pandemics in minimizing the spread of infectious diseases.

Timely Diagnosis of Incubating Syphilis Infections Using Treponema pallidum Transcription-Mediated Amplification Assay.

BACKGROUND: Syphilis is a complex, multistage, sexually transmitted infection (STI) caused by the bacterium Treponema pallidum subspecies pallidum (TP). New diagnostic tools are needed to minimize transmission. In this study, we aimed to assess the additional value of an investigational transcription-mediated amplification test for TP (TP-TMA) for routine diagnostics. METHODS: Between September 2021 and August 2022, visits by all participants of the national preexposure prophylaxis (PrEP) program at the sexual health center (SHC) in Amsterdam were included. Anal, pharyngeal, vaginal, and urine samples collected for Chlamydia trachomatis and Neisseria gonorrhoeae screening were additionally tested with the TP-TMA assay based on detection of 23S rRNA of TP. RESULTS: In total, 9974 SHC visits by 3283 participants were included. There were 191 infectious syphilis cases diagnosed: 26 (14%) primary syphilis, 54 (29%) secondary syphilis, and 111 (58%) early latent syphilis. In 79 of the 191 (41%) syphilis cases, at least 1 sample was TP-TMA-positive. For 16 participants, the positive TP-TMA result was not concordant with routine diagnostics. Of those, 2 participants were treated for syphilis within a week before the visit. Eight participants were treated for a syphilis notification at the visit or for another STI. Five participants were diagnosed with syphilis at the following visit, and 1 participant was lost to follow-up. CONCLUSIONS: By adding the TP-TMA assay to routine diagnostics, we identified 14 of 191 (7%) additional syphilis infections among participants of the national PrEP program. The TP-TMA assay is a useful diagnostic tool to increase syphilis case finding and thus limit the transmission of syphilis.

The impact of COVID-19-related restrictions in 2020 on sexual healthcare use, pre-exposure prophylaxis use, and sexually transmitted infection incidence among men who have sex with men in Amsterdam, the Netherlands.

OBJECTIVES: We studied the effects of restrictions related to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus disease 2019 [COVID-19]) pandemic on the use of sexual healthcare and pre-exposure prophylaxis (PrEP) and on the incidence of sexually transmitted infections (STIs) among men who have sex with men (MSM) in a prospective, open-label PrEP demonstration study (AMPrEP) in Amsterdam, the Netherlands. METHODS: We retrieved data from 2019 to 2020 for participants with one or more study visit in 2019 (n = 305) and from two COVID-19 questionnaires (2020: n = 203; 2021: n = 160). Analyses were stratified for three periods of pandemic-related restrictions (first: 15 March 2020-15 June 2020; second: 16 June 2020-15 September 2020; third: 16 September 2020-31 December 2020 or 1 April 2021 for the COVID-19 questionnaire). Endpoints included returning for care during the pandemic, PrEP use (increased/unchanged vs. deceased/stopped, relative to 2019), and any STI/HIV. We modelled determinants of care and PrEP use via multivariable logistic regression and STI incidence using piecewise Poisson regression, comparing the 2020 and 2019 periods. RESULTS: Of the 305 MSM included in the analysis, 72.8% returned for care during the pandemic, and this was significantly more likely among daily (vs. event-driven) PrEP users (p < 0.001). Increased/unchanged PrEP use ranged from 55.2% to 58.1% across the three pandemic periods and was more likely among those reporting chemsex in the first (p = 0.001) and third (p = 0.020) periods and among those reporting an increased/unchanged number of sex partners during the second period (p = 0.010). STI incidence was significantly lower in 2020 than in 2019 during the first period (incidence rate ratio [IRR] 0.43; 95% confidence interval [CI] 0.28-0.68) and not significantly different during the second (IRR 1.38; 95% CI 0.95-2.00) and third (IRR 1.42; 95% CI 0.86-2.33) periods. No HIV was diagnosed. CONCLUSION: COVID-19-related restrictions coincided with reduced care and PrEP use. Changes in STI incidence suggest delayed diagnoses. Ways to ensure continued access to sexual healthcare during restrictions are needed.

Can we screen less frequently for STI among PrEP users? Assessing the effect of biannual STI screening on timing of diagnosis and transmission risk in the AMPrEP Study.

BACKGROUND: In many countries, HIV pre-exposure prophylaxis (PrEP) users are screened quarterly for STIs. We assessed the consequences of less frequent STI testing. We also assessed determinants of asymptomatic STI and potential for onward transmission. METHODS: Using data from the AMPrEP study, we assessed the proportion of syphilis, and genital, anal, and pharyngeal chlamydia and gonorrhoea diagnoses which would have been delayed with biannual versus quarterly screening. We assessed the potential for onward transmission by examining reported condomless anal sex (CAS) in periods after to-be-omitted visits when screening biannually. We assessed determinants of incident asymptomatic STIs using Poisson regression and calculated individual risk scores on the basis of the coefficients from this model. RESULTS: We included 366 participants. Median follow-up was 47 months (IQR 43-50). 1,183STIs were diagnosed, of which 932(79%) asymptomatic. With biannual screening, 483 asymptomatic STIs (52%) diagnoses would have been delayed at 364 study visits. Of these visits, 129 (35%), 240 (66%) and 265 (73%) were followed by periods of CAS with steady, known casual or unknown casual partners, respectively. Older participants had a lower risk of asymptomatic STI (incidence rate ratio (IRR) 0.86/10-year increase, 95% CI 0.80 to 0.92), while CAS with known (IRR 1.36, 95% CI 1.10 to 1.68) and unknown (IRR 1.86, 95% CI 1.48 to 2.34) casual partners and chemsex (IRR 1.51, 95% CI 1.28 to 1.78) increased the risk. The individual risk scores had limited predictive value (sensitivity=0.70 (95% CI 0.66 to 0.74), specificity=0.50 (95% CI 0.48 to 0.51)). CONCLUSION: Reducing the STI screening frequency to biannually among PrEP users will likely result in delayed diagnoses, potentially driving onward transmission. Although determinants for asymptomatic STIs were identified, predictive power was low.

Treponema pallidum Strains Among Women and Men Who Have Sex With Women in Amsterdam, the Netherlands and Antwerp, Belgium Between 2014 and 2020.

ABSTRACT: The Treponema pallidum strain distribution among men who have sex with women were similar to the strain distribution men who have sex with men. The most prevalent strains and percentage of strains belonging to the Nichols lineage are similar to previous studies in Amsterdam focusing on men who have sex with men.

Leishmania species and clinical characteristics of Pacific and Amazon cutaneous leishmaniasis in Ecuador and determinants of health-seeking delay: a cross-sectional study.

BACKGROUND: Cutaneous Leishmaniasis (CL) affects up to 5.000 people in Ecuador each year. L. guyanensis and L. braziliensis are the most common of the eight CL-causing Leishmania species. Earlier CL research concentrated on the easily accessible Pacific region. This study aims to describe the Leishmania species in Pacific and Amazon ecoregions, to analyze regional differences in CL patient clinical presentation, and to identify determinants of health-seeking delay. METHODS: All cases in this cross-sectional study were diagnosed using smear slide microscopy, PCR, or both. Cytochrome B gene sequencing was used to identify the causative Leishmania species in qPCR-positive samples. RESULTS: This study included 245 patients, with 154 (63%) infected in the Pacific region and 91 (37%) infected in the Amazon. Causative Leishmania species were identified in 135 patients (73% of qPCR positives). L. guyanensis was identified in 76% (102/135) of the samples and L. braziliensis in 19% (26/135). The Pacific region had a low prevalence of 6% (5/89) of L. braziliensis. For the first time, we report L. guyanensis from the central Amazon, L. braziliensis from the northern Pacific, and L. lainsoni from both the central Amazon and northern Pacific. Amazon cases had a longer median health-seeking delay in months (2.0, IQR 3.0) than Pacific cases (1.0, IQR 1.5). Prolonged health-seeking delay was associated with older age, Amerindian ethnicity, infection at lower altitudes, non-ulcerative lesions, and lesions on the lower limbs. CONCLUSIONS: In the Pacific region, health-seeking delay is relatively short and L. braziliensis prevalence remains low. Limited access to health care and stigma might explain the prolonged health-seeking delay in the Amazon. We recommend larger studies on the distribution of Leishmania species in Amazon CL cases and additional regional research into diagnostic test accuracy. Furthermore, the determinants of health-seeking delay in Ecuador should be investigated further.

Multi-sensorial perceptions of risk: the aesthetics behind (muco)cutaneous leishmaniasis-related stigma in Ecuador.

Previous research on the stigma associated with cutaneous leishmaniasis, a vector-transmitted parasitic disease, focuses on aesthetic appearance affectation as the leading cause of stigmatisation. However, Indigenous populations in the hinterland of Amazonian Ecuador trigger stigma expressions by recognising (muco)cutaneous leishmaniasis, primarily through atypical smell, followed by the odd voice sound, appearance and taste. This empirical way of recognising symptoms relies on embodied forms of identifying a disease, contrasting the Western supremacy of visuality and demanding to be understood via multi-sensorial anthropology. Through ethnographic research and data retrieved from eighty-three semistructured interviews and fifteen focus groups in seven Ecuadorian ethnic groups - including six Indigenous groups in the Amazon region - this paper analyses how the sensorium is a health thermometer. Findings reveal that differentiated cultural responses to a sense of peril, contagion and social (self)rejection, understood as stigma expressions, are linked to the holistic approach to health (or well-being) shared by Indigenous populations. In forest societies, well-being is explained through successful (non-)human relationships, and disease permeates through bodies that lack balanced relations.

Sexual transmission of infections across Europe: appraising the present, scoping the future.

Objectives: Our journal partnered with the Europe section of the International Union against STI (IUSTI) at a workshop held at the 18th European AIDS Conference in London on 30 October 2021. The workshop reviewed epidemiological trends and discussed STI care provision within HIV services across Europe. Methods and Results: We started by highlighting trends in bacterial STIs reported to the European Centre for Disease Prevention and Control from countries in the European Union/European Economic Area. This showed that notifications of bacterial STIs reached an all-time high in 2019, but are expected to be impacted by the COVID-19 pandemic in 2020-2021. We then reviewed the evolving relationship between STIs and HIV and pointed out how antiretroviral treatment and pre-exposure prophylaxis remain highly effective against HIV transmission despite the rising incidence of STIs. Within emerging concepts in STIs, we appraised the benefits and risks of asymptomatic screening for chlamydia, and also considered the potential perils of routinely testing for agents that lack a defined role in disease. Finally, we discussed standards of STI care for people living with HIV, informed by a brief survey of IUSTI Europe country representatives and members of the Euroguidelines in Central and Eastern Europe network. Conclusions: The survey indicated substantial variability and identified key improvement targets: fighting barriers to effective service provision and access, increasing diagnostic capability and taking leadership in driving up the quality of care. We must not forget the STI-related needs of the many people who will be living with HIV for decades into the future.

Shigella is common in symptomatic and asymptomatic men who have sex with men visiting a sexual health clinic in Amsterdam.

INTRODUCTION: Shigellosis is a reportable infectious disease. It can present as a severe bloody diarrhoea but is often asymptomatic. Shigella can be sexually transmissible. We performed a study among symptomatic and asymptomatic men who have sex with men (MSM) to assess the prevalence of Shigella, Salmonella and Campylobacter. METHODS: From March to June 2020, MSM attending the Amsterdam centre for sexual health were consecutively included. Predefined minimal numbers of inclusion of 150, 100 and 50 were determined, respectively, for MSM who reported no diarrhoea, diarrhoea during last month or diarrhoea on the day of visit to clinic. Anal samples were tested for the presence of Shigella, Salmonella and Campylobacter. During the same period, the frequency of these bacteria was assessed in routinely tested samples requested by general physicians or nursing home physicians. Characteristics of included MSM were compared between the men with different diarrhoea anamnesis, and the prevalence of shigellosis was estimated in each group. RESULTS: We included 212 MSM without diarrhoea, 109 MSM who recently had diarrhoea and 68 MSM who reported diarrhoea on the day of clinic visit. Thirteen (3.3%, 95% CI 1.7% to 5.6%) MSM were infected with Shigella, none with Salmonella and 7 (1.8%, 95% CI 0.7% to 3.7%) with Campylobacter. Shigella prevalence was 2.8% (95% CI 1.0% to 6.1%) in asymptomatic men, 3.7% (95% CI 1.0% to 9.1%) in men who recently had diarrhoea and 4.4% (95% CI 0.9% to 12.4%) in men with current diarrhoea (p=0.799). Shigella was more frequently found in MSM who had used pre-exposure prophylaxis (PrEP) in the preceding 3 months (10/151), compared with those not having used PrEP (2/146) or being HIV positive (1/75) (p=0.038). Shigella was significantly more often detected among MSM compared with routinely obtained faecal samples being 11/770 (1.4%) (p=0.031). CONCLUSION: Shigella infections are relatively common in both symptomatic and asymptomatic MSM. Future studies should focus on the risk of onward transmission via asymptomatic persons. Samenvatting Introductie Shigellose is een meldingsplichtige infectieziekte. Het kan zich presenteren als een ernstige bloederige diarree, maar is vaak asymptomatisch. Shigella kan seksueel overdraagbaar zijn. We hebben een onderzoek uitgevoerd onder symptomatische en asymptomatische mannen die seks hebben met mannen (MSM) om de prevalentie van Shigella, Salmonella en Campylobacter te bepalen. Methoden Van maart tot juni 2020 werden achtereenvolgens MSM van het Amsterdamse centrum voor seksuele gezondheid opgenomen. Vooraf gedefinieerde minimale aantallen van inclusie van respectievelijk 150, 100 en 50 waren bepaald voor MSM die geen diarree, diarree in de afgelopen maand of diarree op de dag van bezoek aan de kliniek meldden. Anale monsters werden getest op de aanwezigheid van Shigella, Salmonella en Campylobacter. In dezelfde periode werd de frequentie van deze bacteriën bepaald in routinematig geteste monsters aangevraagd door huisartsen of verpleeghuisartsen. Kenmerken van geïncludeerde MSM werden vergeleken tussen mannen met verschillende diarree anamnese, en de prevalentie van shigellose werd in elke groep geschat. Resultaten We includeerden 212 MSM zonder diarree, 109 MSM die onlangs diarree hadden en 68 MSM die diarree meldden op de dag van het bezoek aan de kliniek. Dertien (3,3%, 95% CI 1,7-5,6%) MSM waren geïnfecteerd met Shigella, geen enkele met Salmonella, en 7 (1,8%, 95% CI 0,7-3,7%) met Campylobacter. De prevalentie van Shigella was 2,8% (95%CI 1,0-6,1%) bij asymptomatische mannen, 3,7% (95%CI 1,0-9,1%) bij mannen die recent diarree hadden en 4,4% (95%CI 0,9-12,4%) bij mannen met huidige diarree (P=0,799). Shigella werd vaker gevonden bij MSM die in de voorgaande drie maanden (10/151) PrEP hadden gebruikt dan bij mensen die geen PrEP hadden gebruikt (2/146) of hiv-positief waren (1/75) (p=0,038). Shigella werd significant vaker gedetecteerd bij MSM in vergelijking met routinematig verkregen fecale monsters, namelijk 11/770 (1,4%) (p=0,031). Conclusie Shigella infecties komen relatief vaak voor bij zowel symptomatische als asymptomatische MSM. Toekomstige studies moeten zich richten op het risico van verdere overdracht via asymptomatische personen.

Macrolide-Resistant Mycoplasma genitalium Impairs Clinical Improvement of Male Urethritis After Empirical Treatment.

BACKGROUND: Mycoplasma genitalium (MG) is associated with urethritis in men and could play a role in clinical outcome. We examined clinical improvement of symptoms in men receiving empirical treatment for urethritis and correlated the outcome with Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT), MG, and MG macrolide resistance-associated mutations (MRAM) status. METHODS: At the sexually transmitted infection clinic in Amsterdam, the Netherlands, empirical treatment for gonococcal urethritis is 1 g ceftriaxone and for nongonococcal urethritis 1 g azithromycin. In 2018 to 2019, we tested urine samples of men with urethritis for CT, NG, and MG using transcription-mediated amplification assays. Mycoplasma genitalium-positive samples were tested for MRAM using quantitative polymerase chain reaction. Two weeks after receiving therapy, men were sent a text message inquiring after clinical improvement. RESULTS: We evaluated 2505 cases of urethritis. The positivity rates of NG, CT, and MG were 26% (648 of 2489), 29% (726 of 2489), and 23% (522 of 2288), respectively. In 768 of 2288 of the cases (34%), no causative agent was detected. Most cases were infected with a single pathogen: NG, 417 of 2288 (18%); CT, 486 of 2288 (21%); and MG, 320 of 2288 (14%). The prevalence of MRAM among MG-positives was 74% (327 of 439). For 642 (25.6%) cases, we could evaluate clinical improvement after treatment of whom 127 (20%) indicated no improvement; 9% (15 of 174) in NG cases, 18% (35 of 195) in CT cases, 14% (4 of 28) in MG wild-type cases, and 40% (38 of 94) in MG-MRAM cases. Clinical improvement in MG-MRAM cases was significantly lower compared with all other groups (P < 0.001). CONCLUSIONS: Presence of MG-MRAM is associated with lack of clinical improvement in azithromycin-treated nongonococcal urethritis.

Factors Associated With the Intention to Use HIV Preexposure Prophylaxis for Young and Older Men Who Have Sex With Men.

BACKGROUND: The uptake of preexposure prophylaxis (PrEP) against HIV is low among young men who have sex with men (MSM) in the Netherlands. Studying the intention to use PrEP among non-PrEP using young and older MSM can guide health authorities in developing new prevention campaigns to optimize PrEP uptake. METHODS: We investigated the sociodemographic, behavioral, and psychosocial factors associated with a high PrEP use intention in the coming 6 months among 93 young MSM (aged ≤25 years), participating in an online survey, and 290 older MSM (aged ≥26 years), participating in an open, prospective cohort in 2019 to 2020. RESULTS: Perceiving PrEP as an important prevention tool was associated with a high PrEP use intention among young and older MSM. Among young MSM, a high level of PrEP knowledge and believing that PrEP users take good care of themselves and others were associated with a high PrEP use intention. Among older MSM, 2 or more anal sex partners, chemsex, high HIV risk perception, and believing PrEP increases sexual pleasure were associated with a high PrEP use intention. Believing PrEP leads to adverse effects was associated with a low intention to use PrEP among older MSM. CONCLUSIONS: To conclude, we showed that both behavioral and psychosocial factors were associated with a high PrEP use intention among young and older MSM. In addition to focusing on sexual behavior and HIV risk, future prevention campaigns and counseling on PrEP could incorporate education, endorsing positive beliefs, and disarming negative beliefs to improve the uptake of PrEP in young and older MSM.

Controversies and evidence on Chlamydia testing and treatment in asymptomatic women and men who have sex with men: a narrative review.

BACKGROUND: Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide. CT is mainly asymptomatic. Test-and-treat strategies are widely implemented to prevent transmission and complications. Strategies are not without controversy in asymptomatic women and men who have sex with men (MSM). Concerns are emerging to test and treat asymptomatic persons for urogenital CT ('Controversy 1') and pharyngeal or rectal CT ('Controversy 2'), whereby testing symptomatic persons is not under debate. Opposed views in CT treatment involve using azithromycin versus doxycycline ('Controversy 3'). The objective of this review is to provide coverage of these public health and clinical controversies by reviewing the current scientific evidence. METHODS: A literature search was performed using PubMed for relevant publications between 2018 and September 2021, and iterative retrieval of additional relevant publications. RESULTS: Controversy 1. In women, the majority of asymptomatic CT are at the urogenital site, and detections mostly include viable CT. CT easily transmits to a partner and potentially also between the vaginal and rectal areas; the clinical impact of urogenital CT is established, although risks for adverse outcomes are uncertain. Wide-scale testing in asymptomatic women has not resulted in reduced prevalence. In MSM, evidence for the clinical impact of asymptomatic urogenital CT is lacking. Controversy 2. Rectal CT is common in women diagnosed with urogenital CT, but the clinical impact of asymptomatic rectal CT is uncertain. In MSM, rectal CT is common, and most CT infections are at the rectal site, yet the risk of longer term complications is unknown. In both sexes, pharyngeal CT is uncommon and has no documented clinical impact. Controversy 3. In the treatment of rectal CT, doxycycline has superior effectiveness to azithromycin. Evidence has also accumulated on the harms of test-and-treat strategies. CONCLUSIONS: Current practices vary widely, from widescale test-and-treat approaches to more individual patient- and partner-level case management. Choosing which asymptomatic people to test at what anatomic site, and whether to test or not, requires an urgent (re-)definition of the goals of testing and treating asymptomatic persons. Treatment guidelines are shifting toward universal doxycycline use, and clinical practice now faces the challenge of implementation.

Eligibility criteria vs. need for pre-exposure prophylaxis: a reappraisal among men who have sex with men in Amsterdam, the Netherlands.

To reappraise pre-exposure prophylaxis (PrEP) eligibility criteria towards the men who have sex with men (MSM) with highest HIV-risk, we assessed PrEP need (i.e. HIV-risk) using Amsterdam Cohort Studies data from 2011-2017 for all non-PrEP using MSM. Outcomes were incident HIV-infection and newly-diagnosed anal STI. Determinants were current PrEP eligibility criteria (anal STI and condomless sex (CAS)) and additional determinants (age, education, group sex, alcohol use during sex and chemsex). We used targeted maximum likelihood estimation (TMLE) to estimate the relative risk (RR) and 95% confidence intervals (CI) of determinants on outcomes, and calculated population attributable fractions (PAFs) with 95% CI using RRs from TMLE. Among 810 included MSM, 22 HIV-infections and 436 anal STIs (n = 229) were diagnosed during follow-up. Chemsex (RR = 5.8 (95% CI 2.0-17.0); PAF = 55.3% (95% CI 43.3-83.4)), CAS with a casual partner (RR = 3.3 (95% CI 1.3-8.7); PAF = 38.0% (95% CI 18.3-93.6)) and anal STI (RR = 5.3 (95% CI 1.7-16.7); PAF = 22.0 (95% CI -16.8 to 100.0)) were significantly (P < 0.05) associated with and had highest attributable risk fractions for HIV. Chemsex (RR = 2.0 (95% CI 1.6-2.4); PAF = 19.5 (95% CI 10.6-30.6)) and CAS with a casual partner (RR = 2.5 (95% CI 2.0-3.0); PAF = 28.0 (95% CI 21.0-36.4)) were also significantly associated with anal STI, as was younger age (16-34/≥35; RR = 1.7 (95% CI 1.4-2.1); PAF = 15.5 (95% CI 6.4-27.6)) and group sex (RR = 1.3 (95% CI 1.1-1.6); PAF = 9.0 (95% CI -2.3 to 23.7)). Chemsex should be an additional PrEP eligibility criterion.

Genetic Variation in the MBL2 Gene Is Associated with Chlamydia trachomatis Infection and Host Humoral Response to Chlamydia trachomatis Infection.

This study aims to assess the potential association of MBL2 gene single nucleotide polymorphisms (SNPs) to Chlamydia trachomatis infection. We analysed a selected sample of 492 DNA and serum specimens from Dutch Caucasian women. Women were categorized into four groups of infection status based on the results of DNA and antibody tests for C. trachomatis: Ct-DNA+/IgG+, Ct-DNA+/IgG−, Ct-DNA−/IgG+, and Ct-DNA−/IgG−. We compared six MBL2 SNPs (−619G > C (H/L), −290G > C (Y/X), −66C > T (P/Q), +154C > T (A/D), +161A > G (A/B), and +170A > G (A/C)) and their respective haplotypes in relation to these different subgroups. The −619C (L) allele was less present within the Ct-DNA−/IgG+ group compared with the Ct-DNA−/IgG− group (OR = 0.49; 95% CI: 0.28−0.83), while the +170G (C) allele was observed more in the Ct-DNA+/IgG+ group as compared with the Ct-DNA−/IgG− group (OR = 2.4; 95% CI: 1.1−5.4). The HYA/HYA haplotype was more often present in the Ct-DNA−/IgG− group compared with the Ct-DNA+/IgG+ group (OR = 0.37; 95% CI: 0.16−0.87). The +170G (C) allele was associated with increased IgG production (p = 0.048) in C. trachomatis PCR-positive women. This study shows associations for MBL in immune reactions to C. trachomatis. We showed clear associations between MBL2 genotypes, haplotypes, and individuals' stages of C. trachomatis DNA and IgG positivity.

Cancer Risk Stratification of Anal Intraepithelial Neoplasia in Human Immunodeficiency Virus-Positive Men by Validated Methylation Markers Associated With Progression to Cancer.

BACKGROUND: High-grade anal intraepithelial neoplasia (HGAIN; AIN2-3) is highly prevalent in HIV+ men, but only a minority of these lesions progress towards cancer. Currently, cancer progression risk cannot be established; therefore, no consensus exists on whether HGAIN should be treated. This study aimed to validate previously identified host cell DNA methylation markers for detection and cancer risk stratification of HGAIN. METHODS: A large independent cross-sectional series of 345 anal cancer, AIN3, AIN2, AIN1, and normal control biopsies of HIV+ men was tested for DNA methylation of 6 genes using quantitative methylation-specific PCR. We determined accuracy for detection of AIN3 and cancer (AIN3+) by univariable and multivariable logistic regression analysis, followed by leave-one-out cross-validation. Methylation levels were assessed in a series of 10 anal cancer cases with preceding HGAIN at similar anatomic locations, and compared with the cross-sectional series. RESULTS: Methylation levels of all genes increased with increasing severity of disease (P < .05). HGAIN revealed a heterogeneous methylation pattern, with a subset resembling cancer. ZNF582 showed highest accuracy (AUC = 0.88) for AIN3+ detection, slightly improved by addition of ASCL1 and SST (AUC = 0.89), forming a marker panel. In the longitudinal series, HGAIN preceding cancer displayed high methylation levels similar to cancers. CONCLUSIONS: We validated the accuracy of 5 methylation markers for the detection of anal (pre-) cancer. High methylation levels in HGAIN were associated with progression to cancer. These markers provide a promising tool to identify HGAIN in need of treatment, preventing overtreatment of HGAIN with a low cancer progression risk.

Characterisation of anal intraepithelial neoplasia and anal cancer in HIV-positive men by immunohistochemical markers p16, Ki-67, HPV-E4 and DNA methylation markers.

Human papillomavirus (HPV)-induced anal intraepithelial neoplasia (AIN, graded 1-3) is highly prevalent in HIV-positive (HIV+) men who have sex with men (MSM), but only a minority of lesions progresses to cancer. Our study aimed to characterise comprehensively anal tissue samples from a cross-sectional series (n = 104) of HIV+ MSM and longitudinal series (n = 40) of AIN2/3 progressing to cancer using different biomarkers. The cross-sectional series consisted of 8 normal, 26 AIN1, 45 AIN2, 15 AIN3 and 10 anal squamous cell carcinoma. Tissue sections were immunohistochemically (IHC) stained for p16 (viral transformation marker), Ki-67 (cellular proliferation marker) and HPV-E4 (viral production marker). We evaluated the expression of IHC markers and compared it with DNA methylation, a marker for malignant transformation. E4 positivity decreased, whereas p16 and Ki-67 scores and methylation marker positivity increased (P values < .001) with increasing severity of anal lesions. Within AIN2, a heterogeneous biomarker pattern was observed concerning E4, p16 and methylation status, reflecting the biological heterogeneity of these lesions. In the longitudinal series, all AIN2/3 and carcinomas showed high p16 and Ki-67 expression, strong methylation positivity and occasional E4 positivity. We earlier showed that high methylation levels are associated with progression to cancer. The observed E4 expression in some AIN2/3 during the course of progression to cancer and absence of E4 in a considerable number of AIN1 lesions make the potential clinical significance of E4 expression difficult to interpret. Our data show that IHC biomarkers can help to characterise AIN; however, their prognostic value for cancer risk stratification, next to objective methylation analysis, appears to be limited.

Emergence of a Neisseria gonorrhoeae clone with reduced cephalosporin susceptibility between 2014 and 2019 in Amsterdam, The Netherlands, revealed by genomic population analysis.

BACKGROUND: Emerging resistance to cephalosporins in Neisseria gonorrhoeae (Ng) is a major public health threat, since these are considered antibiotics of last resort. Continuous surveillance is needed to monitor the circulation of resistant strains and those with reduced susceptibility. OBJECTIVES: For the purpose of epidemiological surveillance, genomic population analysis was performed on Ng isolates from Amsterdam with a focus on isolates with reduced susceptibility to ceftriaxone. METHODS: WGS data were obtained from 318 isolates from Amsterdam, the Netherlands between 2014 and 2019. Isolates were typed according to MLST, Ng Multi-Antigen Sequence Typing (NG-MAST) and Ng Sequence Typing for Antimicrobial Resistance (NG-STAR) schemes and additional resistance markers were identified. Phylogenetic trees were created to identify genetic clusters and to compare Dutch and non-Dutch MLST7827 isolates. RESULTS: MLST7363 and MLST1901 were the predominant strains having reduced susceptibility to ceftriaxone during 2014-16; MLST7827 emerged and dominated during 2017-19. NG-STAR38 and NG-MAST2318/10386 were predominant among MLST7827 isolates. MLST7827 reduced susceptibility isolates carried a non-mosaic 13.001 penA allele with an A501V mutation and porB1b G120K/A121D mutations, which were lacking in susceptible MLST7827 isolates. Phylogenetic analysis of all publicly available MLST7827 isolates showed strong genetic clustering of Dutch and other European MLST7827 isolates. CONCLUSIONS: MLST7827 isolates with reduced ceftriaxone susceptibility have emerged during recent years in Amsterdam. Co-occurrence of penA A501V and porB1b G120K/A121D mutations was strongly associated with reduced susceptibility to ceftriaxone. Genetic clustering of Dutch and other European MLST7827 isolates indicates extensive circulation of this strain in Europe. Close monitoring of the spread of this strain having an alarming susceptibility profile is needed.

Sexual consent and chemsex: a quantitative study on sexualised drug use and non-consensual sex among men who have sex with men in Amsterdam, the Netherlands.

BACKGROUND: Chemsex (drug use to enhance sex) has emerged among men who have sex with men (MSM). Non-consensual sex (NCS) is hypothesised to occur frequently under the influence of chemsex, however data are scarce. In this cross-sectional study, it was aimed to assess whether NCS is associated with chemsex. METHODS: We offered a survey about chemsex in the past 6 months (crystal methamphetamine, mephedrone and/or gamma-hydroxybutyrate/gamma-butyrolacton use) and NCS (sexual experiences beyond one's limits or unpleasant sexual experiences) in the past 5 years to Amsterdam-located gay dating platform users. Associations were assessed using χ² test, Fisher's exact test and multivariable logistic regression. RESULTS: Of 891 participants, 30.6% (273 of 891) engaged in chemsex; 21.2% engaging and 16.7% not engaging in chemsex reported any NCS experiences (p=0.109).Among MSM who reported any NCS experiences, chemsex engagers reported being touched against one's will less often compared with non-engagers (22.4% vs 39.8%; p=0.036). Yet, chemsex engagers reported passing out and not remembering what happened during drug use more often (41.4% vs 8.7%; p<0.001). The level of suffering from NCS experiences did not differ between chemsex engagers and non-engagers (p=0.539); and was rated by most participants with no suffering at all or low suffering (77.1%). In the multivariable regression analyses, chemsex engagement in the past 6 months was associated with NCS (adjusted OR 1.46; 95% CI 1.01 to 2.11). CONCLUSIONS: A substantial proportion of MSM (regardless of chemsex engagement) reported NCS in the past 5 years. In multivariate logistic regression analysis, chemsex engagement was associated with an NCS experience. Among participants who reported NCS, suffering related to NCS however, did not differ between chemsex engagers and non-engagers. Sexual healthcare professionals need to address chemsex and NCS during consultations involving MSM and refer men for specialised help if deemed necessary.

Where to go to in chlamydia control? From infection control towards infectious disease control.

OBJECTIVES: The clinical and public health relevance of widespread case finding by testing for asymptomatic chlamydia infections is under debate. We wanted to explore future directions for chlamydia control and generate insights that might guide for evidence-based strategies. In particular, we wanted to know the extent to which we should pursue testing for asymptomatic infections at both genital and extragenital sites. METHODS: We synthesised findings from published literature and from discussions among national and international chlamydia experts during an invitational workshop. We described changing perceptions in chlamydia control to inform the development of recommendations for future avenues for chlamydia control in the Netherlands. RESULTS: Despite implementing a range of interventions to control chlamydia, there is no practice-based evidence that population prevalence can be reduced by screening programmes or widespread opportunistic testing. There is limited evidence about the beneficial effect of testing on pelvic inflammatory disease prevention. The risk of tubal factor infertility resulting from chlamydia infection is low and evidence on the preventable fraction remains uncertain. Overdiagnosis and overtreatment with antibiotics for self-limiting and non-viable infections have contributed to antimicrobial resistance in other pathogens and may affect oral, anal and genital microbiota. These changing insights could affect the outcome of previous cost-effectiveness analysis. CONCLUSION: The balance between benefits and harms of widespread testing to detect asymptomatic chlamydia infections is changing. The opinion of our expert group deviates from the existing paradigm of 'test and treat' and suggests that future strategies should reduce, rather than expand, the role of widespread testing for asymptomatic chlamydia infections.